Optimal age of maturity in fluctuating environments under r‐ and K‐selection

Optimality models for evolution of life histories have shown that increased environmental stochasticity promotes early age of maturity. Here we argue that if r‐selection for early maturation implies a tradeoff making those phenotypes more sensitive to a change in population size than phenotypes maturing at older ages, K‐selection can favor delayed onset of maturation. We analyze a general stochastic Leslie‐matrix model with a simplified density regulation affecting all survivals equally through a function of the population vector, often called the ‘critical age class’. We show that the outcome of such an age‐dependent r‐ and K‐selection is that the expected value of the ‘critical age class’ is maximized by evolution, a strategy strongly influenced by the magnitude of the environmental stochasticity. We also demonstrate that evolution caused by such density‐dependent selection influences the population dynamics, showing a possible reciprocal effect between ecology and evolution in age‐structured populations. This modeling approach reveals that changes in population size affecting the fitness of phenotypes with different age of maturity may be an important selective agent for variation in onset of reproduction in fluctuating environments. This provides a testable hypothesis for how patterns in the population dynamics should affect life history variation.     

Density‐independent reproductive success of the hemiparasitic plant Striga hermonthica,despite positive and negative density‐dependent phases

The hemiparasite Striga hermonthica is a major constraint to smallholder farmer livelihoods and food security in sub‐Saharan Africa. A better understanding of its life‐cycle can help developing more effective management strategies. Here, we studied density dependence in S. hermonthica on Sorghum bicolor. We exposed two genotypes of S. bicolor that differed in the level of tolerance and resistance to S. hermonthica to a range of seed densities of the parasite. We evaluated multiple host and parasite performance parameters through periodic, destructive harvests and related these to the initial seed density using model selection. Initially, the probability for attachment was positively density‐dependent, suggesting facilitation of new infections. However, at host maturity, S. hermonthica infection probability showed strong negative density dependence, indicating severe competition, in particular in the early developmental stages. Although parasite shoot dry weight showed a strong negative density dependence at host maturity, flower production per parasite exhibited positive density dependence again, suggesting compensation. The two host genotypes had similar responses to increased parasite densities, indicating differences between the genotypes in tolerance but not resistance. Consequently, despite density dependence in life‐cycle components, the per capita reproductive output of S. hermonthica, R₀ (flowers seed^?1) was density‐independent. Apparently, management of the hemiparasite can neither benefit from a negatively density‐dependent bottleneck, nor from a positively density‐dependent Allee effect. The most promising suggestion to obtain S. hermonthica population decline (R₀ < 1) and long‐term control is to increase host shading by growing a vigorous, competitive crop.     

Effective size of density‐dependent two‐sex populations: the effect of mating systems

Density dependence in vital rates is a key feature affecting temporal fluctuations of natural populations. This has important implications for the rate of random genetic drift. Mating systems also greatly affect effective population sizes, but knowledge of how mating system and density regulation interact to affect random genetic drift is poor. Using theoretical models and simulations, we compare N_e in short‐lived, density‐dependent animal populations with different mating systems. We study the impact of a fluctuating, density‐dependent sex ratio and consider both a stable and a fluctuating environment. We find a negative relationship between annual N_e/N and adult population size N due to density dependence, suggesting that loss of genetic variation is reduced at small densities. The magnitude of this decrease was affected by mating system and life history. A male‐biased, density‐dependent sex ratio reduces the rate of genetic drift compared to an equal, density‐independent sex ratio, but a stochastic change towards male bias reduces the N_e/N ratio. Environmental stochasticity amplifies temporal fluctuations in population size and is thus vital to consider in estimation of effective population sizes over longer time periods. Our results on the reduced loss of genetic variation at small densities, particularly in polygamous populations, indicate that density regulation may facilitate adaptive evolution at small population sizes.     

LIFE‐HISTORY EVOLUTION AND DENSITY‐DEPENDENT GROWTH IN EXPERIMENTAL POPULATIONS OF YEAST

We studied the evolution of the correlation between growth rate r and yield K in experimental lineages of the yeast Saccharomyces cerevisiae. First, we isolated a single clone every approximately 250 generations from each of eight populations selected in a glucose‐limited medium for 5000 generations at approximately 6.6 population doublings per day (20 clones per line × 8 lines) and measured its growth rate and yield in a new, galactose‐limited medium (with ～1.3 doubling per day). For most lines, r on galactose increased throughout the 5000 generations of selection on glucose whereas K on galactose declined. Next, we selected these 160 glucose‐adapted clones in the galactose environment for approximately 120 generations and measured changes in r and K in galactose. In general, growth rate increased and yield declined, and clones that initially grew slowly on galactose improved more than did faster clones. We found a negative correlation between r and K among clones both within each line and across all clones. We provide evidence that this relationship is not heritable and is a negative environmental correlation rather than a genetic trade‐off.     

Evolutionary tracking is determined by differential selection on demographic rates and density dependence

Recent ecological forecasts predict that ~25% of species worldwide will go extinct by 2050. However, these estimates are primarily based on environmental changes alone and fail to incorporate important biological mechanisms such as genetic adaptation via evolution. Thus, environmental change can affect population dynamics in ways that classical frameworks can neither describe nor predict. Furthermore, often due to a lack of data, forecasting models commonly describe changes in population demography by summarizing changes in fecundity and survival concurrently with the intrinsic growth rate (r). This has been shown to be an oversimplification as the environment may impose selective pressure on specific demographic rates (birth and death) rather than directly on r (the difference between the birth and death rates). This differential pressure may alter population response to density, in each demographic rate, further diluting the information combined to produce r. Thus, when we consider the potential for persistence via adaptive evolution, populations with the same r can have different abilities to persist amidst environmental change. Therefore, we cannot adequately forecast population response to climate change without accounting for demography and selection on density dependence. Using a continuous‐time Markov chain model to describe the stochastic dynamics of the logistic model of population growth and allow for trait evolution via mutations arising during birth events, we find persistence via evolutionary tracking more likely when environmental change alters birth rather than the death rate. Furthermore, species that evolve responses to changes in the strength of density dependence due to environmental change are less vulnerable to extinction than species that undergo selection independent of population density. By incorporating these key demographic considerations into our predictive models, we can better understand how species will respond to climate change.     

Evolution under pH stress and high population densities leads to increased density-dependent fitness in the protist Tetrahymena thermophila

Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist species Tetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r₀). Overall, evolution at low pH led to the convergence of r₀ and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation between r₀ and α, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase in r₀, or decrease of α, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress.     

Selection for life‐history traits to maximize population growth in an invasive marine species

Species establishing outside their natural range, negatively impacting local ecosystems, are of increasing global concern. They often display life‐history features characteristic for r‐selected populations with fast growth and high reproduction rates to achieve positive population growth rates (r) in invaded habitats. Here, we demonstrate substantially earlier maturation at a 2 orders of magnitude lower body mass at first reproduction in invasive compared to native populations of the comb jelly Mnemiopsis leidyi. Empirical results are corroborated by a theoretical model for competing life‐history traits that predicts maturation at the smallest possible size to optimize r, while individual lifetime reproductive success (R₀), optimized in native populations, is near constant over a large range of intermediate maturation sizes. We suggest that high variability in reproductive tactics in native populations is an underappreciated determinant of invasiveness, acting as substrate upon which selection can act during the invasion process.     

Population Dynamics of Evolutionary Change: Demographic Parameters as Indicators of Fitness

I evaluated demographic parameters as indicators of fitness by calculating the net reproductive rate (R₀), exponential rate of change (r), lifetime reproductive success (LRS), and Malthusian parameter (m) for nine genotypes and four phenotypes (two alleles at each of two independent loci) of an age-structured population. The given starting conditions included age-specific survival rates of males and females and age-specific fecundity of females for each genotype (to simplify the problem I presumed no differences in survivorship or fecundity of genotypes with the same phenotype) and the same age structure for each genotype. The prevailing genotype had the greatestm, but it did not have the greatestr,R₀, or LRS, or even the greatest survivorship of either juveniles or adults, or the greatest fecundity. This result indicates thatmis the only correct measure of fitness (i.e., as a predictor of which genotype should prevail from among a group of genotypes) and that comparisons ofr,R₀, LRS, juvenile or adult survival rates, or fecundity may be misleading indicators of which genotype should prevail (i.e., be most “fit”) over time (i.e., be selected for).     

Impact of inter‐ and intra‐specific competition among larvae on larval,adult, and life‐table traits of Aedes aegypti and Aedes albopictus females

1. Few studies have taken a comprehensive approach of measuring the impact of inter‐ and intra‐specific larval competition on adult mosquito traits. In this study, the impact of competition among Aedes aegypti (L.) and A. albopictus (Skuse) was quantified over the entire life of a cohort. 2. Competitive treatments affected hatch‐to‐adult survivorship and the development time to adulthood of females for both species but affected the median wing length of females only for A. albopictus. Competitive treatments had no significant effect on the median adult female longevity nor were there any effects on other individual traits related to blood feeding and reproductive success. 3. Analysis of life table traits revealed no effect of competitive treatment on the net reproductive rate (R₀) but there were significant effects on the cohort generation time (T_c) and the cohort rate of increase (r) for both species. 4. Inter‐ and intra‐specific competition among Aedes larvae may produce individual and population‐level effects that are manifest in adults; however, benign conditions may enable resulting adults to compensate for some impacts of competition, particularly those affecting blood‐feeding success, fecundity, and the net reproductive rate, R₀. The effect of competition, therefore, affects primarily larva‐to‐adult survivorship and the larval development time, which in turn impacts the cohort generation time, T_c, and ultimately the cohort rate of increase, r. 5. The lack of effects of the larval rearing environment on adult longevity suggests that effects on vectorial capacity owing to longevity may be limited if adults have easy access to sugar and bloodmeals.     

Posttranslational oxidative modification of (R)‐2‐(2,4‐dichlorophenoxy)propionate/α‐ketoglutarate‐dependent dioxygenases (RdpA) leads to improved degradation of 2,4‐dichlorophenoxyacetate (2,4‐D)

Microbial activities and the versatility gained through adaptation to xenobiotic compounds are the main biological forces to counteract environmental pollution. The current results present a new adaptive mechanism that is mediated through posttranslational modifications. Strains of Delftia acidovorans incapable of growing autochthonously on 2,4‐dichlorophenoxyacetate (2,4‐D) were cultivated in a chemostat on 2,4‐D in the presence of (R)‐2‐(2,4‐dichlorophenoxy)propionate. Long‐term cultivation led to enhanced 2,4‐D degradation, as demonstrated by improved values of the Michaelis–Menten constant K_m for 2,4‐D and the catalytic efficiency k_cat/K_m of the initial degradative key enzyme (R)‐2‐(2,4‐dichlorophenoxy)propionate/α‐ketoglutarate‐dependent dioxygenases (RdpA). Analyses of the rdpA gene did not reveal any mutations, indicating a nongenetic mechanism of adaptation. 2‐DE of enzyme preparations, however, showed a series of RdpA forms varying in their pI. During adaptation increased numbers of RdpA variants were observed. Subsequent immunoassays of the RdpA variants showed a specific reaction with 2,4‐dinitrophenylhydrazine (DNPH), characteristic of carbonylation modifications. Together these results indicate that posttranslational carbonylation modified the substrate specificity of RdpA. A model was implemented explaining the segregation of clones with improved degradative activity within the chemostat. The process described is capable of quickly responding to environmental conditions by reversibly adapting the degradative potential to various phenoxyalkanoate herbicides.     

Heritability of anti‐predatory traits: vigilance and locomotor performance in marmots

Animals must allocate some proportion of their time to detecting predators. In birds and mammals, such anti‐predator vigilance has been well studied, and we know that it may be influenced by a variety of intrinsic and extrinsic factors. Despite hundreds of studies focusing on vigilance and suggestions that there are individual differences in vigilance, there have been no prior studies examining its heritability in the field. Here, we present one of the first reports of (additive) genetic variation in vigilance. Using a restricted maximum likelihood procedure, we found that, in yellow‐bellied marmots (Marmota flaviventris), the heritability of locomotor ability (h² = 0.21), and especially vigilance (h² = 0.08), is low. These modest heritability estimates suggest great environmental variation or a history of directional selection eliminating genetic variation in these traits. We also found a significant phenotypic (r_P = ?0.09 ± 0.04, P = 0.024) and a substantial, but not significant, genetic correlation (r_A = ?0.57 ± 0.28, P = 0.082) between the two traits (slower animals are less vigilant while foraging). We found no evidence of differential survival or longevity associated with particular phenotypes of either trait. The genetic correlation may persist because of environmental heterogeneity and genotype‐by‐environment interactions maintaining the correlation, or because there are two ways to solve the problem of foraging in exposed areas: be very vigilant and rely on early detection coupled with speed to escape, or reduce vigilance to minimize time spent in an exposed location. Both strategies seem to be equally successful, and this ‘locomotor ability‐wariness’ syndrome may therefore allow slow animals to compensate behaviourally for their impaired locomotor ability.     

Life‐history evolution under fluctuating density‐dependent selection and the adaptive alignment of pace‐of‐life syndromes

We present a novel perspective on life‐history evolution that combines recent theoretical advances in fluctuating density‐dependent selection with the notion of pace‐of‐life syndromes (POLSs) in behavioural ecology. These ideas posit phenotypic co‐variation in life‐history, physiological, morphological and behavioural traits as a continuum from the highly fecund, short‐lived, bold, aggressive and highly dispersive ‘fast’ types at one end of the POLS to the less fecund, long‐lived, cautious, shy, plastic and socially responsive ‘slow’ types at the other. We propose that such variation in life histories and the associated individual differences in behaviour can be explained through their eco‐evolutionary dynamics with population density – a single and ubiquitous selective factor that is present in all biological systems. Contrasting regimes of environmental stochasticity are expected to affect population density in time and space and create differing patterns of fluctuating density‐dependent selection, which generates variation in fast versus slow life histories within and among populations. We therefore predict that a major axis of phenotypic co‐variation in life‐history, physiological, morphological and behavioural traits (i.e. the POLS) should align with these stochastic fluctuations in the multivariate fitness landscape created by variation in density‐dependent selection. Phenotypic plasticity and/or genetic (co‐)variation oriented along this major POLS axis are thus expected to facilitate rapid and adaptively integrated changes in various aspects of life histories within and among populations and/or species. The fluctuating density‐dependent selection POLS framework presented here therefore provides a series of clear testable predictions, the investigation of which should further our fundamental understanding of life‐history evolution and thus our ability to predict natural population dynamics.     

Giving‐up densities and ideal pre‐emptive patch use in a predatory benthic stream fish

1. We used observational and experimental field studies together with an individual‐based simulation model to demonstrate that behaviours of mottled sculpin (Cottus bairdi) were broadly consistent with the expectations of Giving‐Up Density theory and an Ideal Pre‐emptive Distribution habitat selection model. 2. Specifically we found that: (i) adult mottled sculpin established territories within patches characterised by significantly higher prey densities and prey renewal rates than patches occupied by juveniles or randomly selected patches; (ii) patches abandoned by adult sculpin possessed significantly lower prey densities than newly occupied patches, although this was not true for juveniles; (iii) the observed giving‐up density (GUD) for adult sculpin (i.e. average prey density in patches recently abandoned) increased linearly with increasing fish size up to the average prey density measured in randomly selected patches (i.e. 350 prey items per 0.1 m²) and decreased with increasing sculpin density and (iv) juveniles rapidly shifted their distribution towards the highest quality patches following removal of competitively dominant adult sculpin. 3. These results provide the first evidence of the applicability of GUD theory to a stream‐dwelling organism, and they elucidate the underlying factors influencing juvenile and adult sculpin habitat selection and movement behaviours. Furthermore, optimal patch use, ideal pre‐emptive habitat selection and juvenile ‘floating’ provide behavioural mechanisms linking environmental heterogeneity in the stream benthos to density‐dependent regulation of mottled sculpin populations in this system.     

The ontogeny of cross‐sex genetic correlations: an analysis of patterns

The independent evolution of males and females is typically constrained by shared genetic variance. Despite substantial research, we still know little about the evolution of cross‐sex genetic covariance and its standardized measure, the cross‐sex genetic correlation (r_MF). In particular, it is unclear if r_MF tend to vary with age. We compiled 28 traits for which ontogenetic trends in r_MF were documented. Decreases in r_MF with age were observed significantly more often than increases and the mean effect size for the relationship between r_MF and age was large and negative. This suggests that sexual dimorphism (SD) may typically evolve more readily for phenotypes expressed later in ontogeny and that evolutionary inferences related to the evolution of SD should be limited to the ontogenetic stage at which r_MF was estimated. Knowledge about ontogenetic variation in r_MF should help improving our understanding of evolutionary patterns related to SD and the resolution of intralocus sexual conflicts.     

Haplotype‐based genotyping‐by‐sequencing in oat genome research

In a de novo genotyping‐by‐sequencing (GBS) analysis of short, 64‐base tag‐level haplotypes in 4657 accessions of cultivated oat, we discovered 164741 tag‐level (TL) genetic variants containing 241224 SNPs. From this, the marker density of an oat consensus map was increased by the addition of more than 70000 loci. The mapped TL genotypes of a 635‐line diversity panel were used to infer chromosome‐level (CL) haplotype maps. These maps revealed differences in the number and size of haplotype blocks, as well as differences in haplotype diversity between chromosomes and subsets of the diversity panel. We then explored potential benefits of SNP vs. TL vs. CL GBS variants for mapping, high‐resolution genome analysis and genomic selection in oats. A combined genome‐wide association study (GWAS) of heading date from multiple locations using both TL haplotypes and individual SNP markers identified 184 significant associations. A comparative GWAS using TL haplotypes, CL haplotype blocks and their combinations demonstrated the superiority of using TL haplotype markers. Using a principal component‐based genome‐wide scan, genomic regions containing signatures of selection were identified. These regions may contain genes that are responsible for the local adaptation of oats to Northern American conditions. Genomic selection for heading date using TL haplotypes or SNP markers gave comparable and promising prediction accuracies of up to r = 0.74. Genomic selection carried out in an independent calibration and test population for heading date gave promising prediction accuracies that ranged between r = 0.42 and 0.67. In conclusion, TL haplotype GBS‐derived markers facilitate genome analysis and genomic selection in oat.     

Enhanced diastereoselective synthesis of t‐Butyl 6‐cyano‐(3R,5R)‐dihydroxyhexanoate by using aldo‐keto reductase and glucose dehydrogenase co‐producing engineered Escherichia coli

t‐Butyl 6‐cyano‐(3R,5R)‐dihydroxyhexanoate ((3R,5R)‐ 2 ) is a key chiral diol precursor of atorvastatin calcium (Lipitor®). We have constructed a Kluyveromyces lactis aldo‐keto reductase mutant KlAKR‐Y295W/W296L (KlAKRm) by rational design in previous research, which displayed high activity and excellent diastereoselectivity (de_p > 99.5%) toward t‐butyl 6‐cyano‐(5R)‐hydroxy‐3‐oxohexanoate ((5R)‐ 1 ). To realize in situ cofactor regeneration, a robust KlAKRm and Exiguobacterium sibiricum glucose dehydrogenase (EsGDH) co‐producer E. coli BL 21(DE3) pETDuet‐esgdh (MCS1)/pET‐28b (+)‐klakrm was constructed in this work. Under the optimized conditions, AKR and GDH activities of E. coli BL 21(DE3) pETDuet‐esgdh (MCS1)/pET‐28b (+)‐klakrm peaked at 249.9 U/g DCW (dry cellular weight) and 29100 U/g DCW, respectively. It completely converted (5R)‐ 1 at substrate loading size of up to 60.0 g/L (5R)‐ 1 in the absence of exogenous NADH, which was one‐fifth higher than that of the separately prepared KlAKRm and EsGDH under the same conditions. In this manner, a biocatalytic process for (3R,5R)‐ 2 with productivity of 243.2 kg/m³ d was developed. Compared with the combination of separate expressed KlAKRm with EsGDH, co‐expression of KlAKRm and EsGDH has the advantages of alleviating cell cultivation burden and elevating substrate load. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1235–1242, 2017     

Polyoxometalate‐Derived Ultrasmall Pt2W/WO3 Heterostructure Outperforms Platinum for Large‐Current‐Density H2 Evolution

Platinum (Pt)‐based catalysts with high Pt utilization efficiency for efficient H₂ evolution are attracting extensive attention to meet the issues of energy exhaustion and environmental pollution. Herein, a one‐step electrochemical method is demonstrated to construct ultrafine heterostructure Pt₂W/WO₃ on reduced graphene oxide (RGO) by injecting multielectrons into the Preyssler anion [NaP₅W₃₀O₁₁₀]^14? to codeposit with anodic deliquescent Pt cations. The resulting Pt₂W/WO₃/RGO shows much higher performance than that of commercial Pt catalysts for large‐current‐density H₂ evolution, which can deliver a large current density of 500 mA cm^?2 with an overpotential of only 394 mV, much lower than that of 20% Pt/C (578 mV). Comparisons with control experiments and density functional theory (DFT) calculations both suggest that the much enhanced activity can be mainly attributed to the synergistic cooperation of different components to drive fast and continuous hydrogen desorption on Pt₂W/WO₃/RGO, while it could not run normally for 20% Pt/C under similar conditions due to the formation of huge bubbles on the electrode surface. The effective integration of high catalytic activity and hydrogen desorption ability into a single material can yield advanced materials for large‐current‐density H₂ evolution with remarkable stability.     

Positive selection of IL‐33 in adaptive immunity of domestic Chinese goats

The identification of the candidate genes that play key role in phenotypic variation in livestock populations can provide new information about evolution and positive selection. IL‐33 (71954) (Interleukin) gene is associated with the increased nematode resistance in small ruminants; however, the role of IL‐33 for the genetic control of different diseases in Chinese goat breeds is poorly described in scientific literature. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single‐nucleotide polymorphism in IL‐33 gene. Fixation Index (F_ST)‐based method was used for the outlier loci determination and found that IL‐33 was present in outlier area with the provisional combined allocation of mean heterozygosity and F_ST. Positively selected IL‐33 gene was significantly, that is, p(Simul F_ST < sample F_ST = 0.98*) present in corresponding positive selection area. Hence, our study provided novel information about the nucleotide variations in IL‐33 gene and found to be nonsynonymous which may helpful for the genetic control of diseases by enhancing the immune system in local Chinese goat breeds as well as in other analyzed vertebrate species.     

Spatiotemporal mating pattern variation in a wind‐pollinated Mediterranean shrub

Spatiotemporal variation in mating patterns is poorly known in wind‐pollinated plant species. Here, we analysed mating patterns of the wind‐pollinated dioecious shrub Pistacia lentiscus by genotyping 904 seeds from 30 mother plants with eight microsatellite markers in a high‐density population in two consecutive flowering seasons. We found significant differences in some mating system estimates between years, particularly in the levels of correlated paternity. Overall, within‐mothers correlated paternity was higher in 2007 than in 2006 (r_pWM = 0.085 and 0.030), which translated into an effective number of fathers (N_ep) of 11.8 and 33.6 respectively. Using a smoothing interpolation technique, we show that the effective pollen cloud was spatially structured in patches of high‐ and low‐genetic diversity, which do not remain constant from year to year. In 2006, the among‐mothers correlated paternity (r_pAM) showed no trend with distance, suggesting no restriction of pollen dispersal. However, in 2007, r_pAM was greater than zero at short distances, revealing the existence of small‐scale patterns of pollen dispersal. The fact that the studied seasons were climatically homogeneous during the flowering time suggested that the observed differences might be ascribed to between‐year phenological variation of individuals in the studied population or other (unknown) factors. Numerical simulations, based on the real data set, indicated that the clumping of males and decreasing plant density, which is related to different types of pollen limitation, greatly increase correlated mating in this wind‐pollinated species, which is of relevance under the frame of the continuous anthropogenic habitat disturbance suffered by Mediterranean ecosystems.     

Chiral syntheses of methyl (R)‐2‐Sulfanylcarboxylic esters and acids with optical purity determination using HPLC

Accessible chiral syntheses of 3 types of (R)‐2‐sulfanylcarboxylic esters and acids were performed: (R)‐2‐sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and acid (39%, 96%ee), (R)‐2‐sulfanylsucciinic diester (59%, 96%ee), and (R)‐2‐mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and robust method involves (i) clean S_N2 displacement of methanesulfonates of (S)‐2‐hydroxyesters by using commercially available AcSK with tris(2‐[2‐methoxyethoxy])ethylamine and (ii) sufficiently mild deacetylation. The optical purity was determined by the corresponding (2R,5R)‐trans‐thiazolidin‐4‐one and (2S,5R)‐cis‐thiazolidin‐4‐one derivatives based on accurate high‐performance liquid chromatography analysis with high‐resolution efficiency. Compared with the reported method utilizing AcSCs (generated from AcSH and CsCO₃), the present method has several advantages, that is, the use of odorless AcCOSK reagent, reasonable reaction velocity, isolation procedure, and accurate, reliable optical purity determination. The use of accessible AcSK has advantages because of easy‐to‐handle odorless and hygroscopic solid that can be used in a bench‐top procedure. The Ti(OiPr)₄ catalyst promoted smooth trans‐cyclo‐condensation to afford (2R,5R)‐trans‐thiazolidin‐4‐one formation of (R)‐2‐sulfanylcarboxylic esters with available N‐(benzylidene)methylamine under neutral conditions without any racemization, whereas (2S,5R)‐cis‐thiazollidin‐4‐ones were obtained via cis‐cyclo‐condensation and no catalysts. Direct high‐performance liquid chromatography analysis of methyl (R)‐mandelate was also performed; however, the resolution efficiency was inferior to that of the thaizolidin‐4‐one derivatizations.