An Efficient Synthetic Method for (±)-Malyngolide and Its Optical Resolution

A convenient synthetic method for (±)-malyngolide (1), an antibiotic from the marine bluegreen alga Lyngbya majuscula GOMONT, is described. The compound (±)-1 was synthesized from 2-methylglutaric anhydride (starting material) in four steps, involving the TBHP-based osmium-catalyzed procedure for vicinal dihydroxylation of the methylene unit in unsaturated carboxylic acid as the key step. The optical resolution of (±)-l was accomplished by HPLC, in which diastereomeric (+)-2-(4-chlorophenyl)isovaleric acid [(+)-CPIA] esters of (±)-l derived from (+)-CPIA-C1 could be easily separated, and subsequent hydrolysis of each ester gave the enantiomeri-cally pure (?)-l and (+)-l, respectively. A synthetic method for α-methylene malyngolide, which is to be expected for biological activity, is also described.     

Microbial Resolution of (±)-1 and 2-Decalols

By microorganisms or esterase they produce, (±)-1 and 2-decalyl acetates were asymmetrically hydrolyzed to (?)-1-(R)-trans,cis-1-decalol (IIa), (+)-1-(S)-cis,cis-1-decalol (IIIb), (+)-1-(R)-cis,trans-1-decalol (IVa) and (+)-1-(S)-trans,trans-2-decalol (VIIb), (?)-cis,cis-2-decalol (IXb) with the acetates of their antipodes, whereas the axial acetates of (±)-decalols were scarecely hydrolyzed.     

Synthesis of (±)-Homosarkomycin and (±)-Rosaprostol

(±)-Homosarkomycin (2) and (±)-rosaprostol (3) were synthesized from (±)-methyl 2-oxo-bicyclo[3.1.0]hexane-1-carboxylate (1) by using the nucleophilic ring opening reaction on the double-activated cyclopropane ring as the key step.     

Synthesis of (±)-Lamprolobine and (±)-Epilamprolobine

(±)-Lamprolobine, the (+)-enatiomer of which was isolated from the leaves of Lamprolobium fruticosum, and (±)-epilamprolobine were synthesized from δ-valerolactam.     

Resolution of (±)– Cytallene — A Highly Active Anti-HIV Agent with Axial Dissymmetry

Abstract

Anti-HIV agent (±)-cytallene (1b + 2b) was resolved by enantioselective acylation of (±)-N⁴-benzoylcytallene (1d + 2d) with vinyl butyrate in tetrahydrofuran catalyzed by lipase AK from Pseudomonas sp. and subsequent deacylation of 4d and 1d with ammonia in methanol. Optically pure enantiomers 1b and 2b were obtained.     

Enzymic Resolution of (± )-Unsaturated Cyclic Terpene Alcohols via Asymmetric Hydrolysis of Corresponding Acetates by Microorganisms

Asymmetric hydrolysis of the acetates of (±)-cis and trans-carveols by microorganisms or their esterase produced chiral cis and trans-carveols and the acetates of their enantiomers. The enantioselectivity of the microbial hydrolysis and the optical purities of the products varied with the species of microorganisms. This method was also applied in separation of diastereomeric mixtures of (?)-carveols and (?)-7-epi-α-cyperols.     

Synthesis of (±)-Xanthoxins

The enzymatic properties of P2-2 enzyme were determined by using cells of M. radiodurans. The enzyme was: most active at 60°C incubation temperature, stable at 40°C in neutral buffer, and inactivated by heating at 80°C for 15min. Maximal lytic activity occurred at pH 8.5 in Tris-HCl buffer. The range of enzyme stability was between pH 5.5 and 8. Bivalent metal ions, p-chloromercuribenzoate and monoiodo acetate inhibited lytic activity. The molecular weight was estimated to be 16,000 daltons by gel filtration on Sephadex G-75. The enzymatic digestion of peptidoglycans from the cell walls of M. radiodurans and M. lysodeikticus liberated free amino groups, but neither reducing groups nor N-acetylhexosamine, indicating that the enzyme was an endopeptidase. From analysis of the N-terminal amino acids of the digests, it is suggested that the P2-2 enzyme cleaves the peptide bond at the carboxyl group of D-alanine in peptidoglycan.     

Synthesis of (±)-licarin-B

The synthesis of (±)-licarin-B, a neolignan of Licaria aritu Ducke (Lauraceae), was achieved by pyrolysis of 3-hydroxy-3-piperonyl-1-propyl-2-methoxy-4-(E)-propenylphenyl ethers.     

Syntheses of (±)-Epoformin (Desoxyepoxydon) and (±)-Epiepoformin (Desoxyepiepoxydon)

Boron is an essential nutrient for plants, but it is toxic in excess. Transgenic rice plants expressing an Arabidopsis thaliana borate efflux transporter gene, AtBOR4, at a low level exhibited increased tolerance to excess boron. Those lines with high levels of expression exhibited reduced growth. These findings suggest a potential of the borate transporter BOR4 for the generation of high-boron tolerant rice.     

Synthesis of (±)-Hydroxytremetone

(±)Hydroxytremetone (III) has been synthesized from 2-(α-hydoxyisopropyl)-6-hydroxycoumaran (V b) via its O-acetate V c by dehydration with phosphorus tribromide in pyridine solution, followed by acylation with a mixture of trifluoroacetic anhydride and acetic acid. Isohydroxytremetone (IX b) was also synthesized.     

Optical Resolution and Biological Activities of α-Ionylideneacetic Acid.

Nuclease activity associated with cells and protoplasts was analyzed by agarose gel electrophoresis. Datura innoxia protoplasts were found to possess a high exonuclease activity. On the other hand, Datura innoxia cells had an endonuclease activity, but no apparent exonuclease. The exonucleases from the protoplasts were active at pH 5 and 6, but not at pH 9. Endonuclease activity from the cells was also inhibited at pH 9. Cultured cells of Daucus carota, Glycine max, Pisum sativum and Vicia hajastana had endonuclease activity, but did not exhibit exonuclease activity. Nicotiana suaveolens cells had both types of nuclease activity. On the other hand, cells from cereals such as Triticum monococcum, Oryza sativa, and Zea mays had active exonuclease activity.     

Synthesis of ( ± )-Methyl Epijasmonate and ( ± )-Methyl Cucurbate

A novel synthesis of ( ± )-methyl epijasomonate (2) and the first synthesis of ( ± )-methyl cucurbate (4) were achieved starting from 2-allylcyclohexane-1,3-dione (8). The synthetic epimer 2 had a stronger jasmin flavor than the trans-isomer 1 with 95% purity.     

Lipase-Catalyzed Kinetic Resolution of (±)-cis-Flavan-4-ol and Its Acetate: Synthesis of Chiral 3-Hydroxyflavanones

Lipase-catalyzed kinetic resolution of (±)-cis-flavan-4-ol and its acetate led to enantiomerically enriched flavan-4-ol and its acetate. These chiral compounds were converted to (2R, 3R)- and (2S, 3S)-3-hydroxyflavanones.     

Total synthesis of (±)-elegansidiol, (±)-farnesiferol B,and (±)-farnesiferol D

The racemic total synthesis of elegansidiol, farnesiferol B, and farnesiferol D has been obtained following a Diels–Alder approach. Gillman addition, cross metathesis reaction are the other key steps involved in the target synthesis.     

Enzymatic Resolution of (±)-Epoxy-β-cyclogeraniol,a Synthetic Precursor for Abscisic Acid Analogs

Lipase-catalyzed optical resolution of (±)-epoxy-β-cyclogeraniol (1), a key synthetic intermediate for epoxy-β-ionylideneacetic acid, was achieved in high enantiomeric purity. Transesterification with vinyl acetate by using lipase P (Nagase) made enriched (-)-1, while hydrolysis of the corresponding acetate by using lipase P (Amano) afforded (+)-1 with a high E value (E=1600).     

Synthesis of (±)-Tubaic Acid

An alternative synthesis of (±)-tubaic acid (I), a key intermediate compound of rotenone synthesis, has been accomplished by the Wittig reaction.     

A Total Synthesis of (±)-Pachyrrhizone

We examined whether developing cotyledons of soybean seed had photosynthetic activities. The cotyledons evolved oxygen under illumination and the activity was inhibited by 3-(3′,4′-dichlorophenyl)-1,1-dimethylurea. The rate of oxygen evolution decreased during the development of seeds; about 30μ miol O₂ · mg chlorophyll^-1 · hr^-1 at the early developing stage and about 10μ miol O₂-mg chlorophyll^-1 · hr^-1 at the late developing stage. The rate of oxygen uptake remained at an almost constant level of 40^mol 0₂-mg chlorophyll^-1 · hr^-1 throughout the development. Photosynthetic ¹⁴CO₂-fixation by the cotyledon was observed. Ribulose bisphosphate carboxylase was immunochemically detected in the developing cotyledons. These results show that functional photosynthetic apparatus is present in the developing cotyledons of soybean seeds.     

Resolution of (±)-trans-2-phenylcyclohexan-1-ol by lipases from Candida rugosa: effect of catalyst source and reaction conditions

Candida rugosa lipase resolved trans-2-phenylcyclohexan-1-ol. A commercial and a laboratory preparation were compared and better results were obtained with the latter (E >200). Both enzyme preparations were strongly dependent on the substrate concentration for their enantioselectivity. This effect could be due to the presence of an esterase activity unspecific for trans-2-phenylcyclohexan-1-ol. © Rapid Science Ltd. 1998