What was the evolutionary synthesis?

There has not been another scientific revolution that caused as much turmoil and dissension as the darwinian one. For almost 80 years it was again and again pronounced to be a failure and to be totally refuted, and at least three major alternatives were proposed to replace it. Yet, in the 1930s-1940s the opposing views were quickly and decisively refuted and a largely unified evolutionary theory emerged. Why and how this happened, however, is still rather controversial.     

Asymmetric synthesis ofα-aminophosphonic acids

Summary The enantiospecific synthesis of several-aminophosphonic esters starting from enantiomerically pure derivatives of phosphonic analogues of homoserine is reported.     

Enzymatic synthesis of 2′-deoxyadenosine

Summary The title compound was prepared by a two step enzymatic procedure consisting of DNA hydrolysis to the mixture of 2-deoxynucleosides followed by a transdeoxyribosilation of exogenous adenine.     

Biopolitics: the newest synthesis?

On first impression, the disciplines of genetics and political science would appear to be unrelated. And yet, commencing more than 30 years ago, the interdisciplinary field known as Biopolitics has now taken hold. This essay traces the central thrust of the biopolitical research agenda. It describes, analyzes, and assesses how political scientists have sought to show connections between our species' genetic constitution and our species' political behavior. Important bridges between the two are the neurophysiology of the human brain and the role of evolutionary theory in charting man's adaptational political profile. The parameters of the emerging biopolitical literature raise profound policy questions, some of which are also characterized. This revised version was published online in August 2006 with corrections to the Cover Date.     

Stereospecific synthesis of α-methylated amino acids

Summary. Both 2,5-trans and 2,5-cis disubstituted 2-tert-butyl-5-(indol-3-yl)methylimidazolidin-4-ones were synthesised and their enolates were prepared using LDA. While the enolate of the 2,5-trans disubstituted derivative could not be methylated, the enolate of the cis-2,5-disubstituted derivative was successfully methylated with methyl iodide to a product which on hydrolysis gave enantiomerically pure α-methyl-L-tryptophan. Received October 31, 1998, Accepted July 23, 1999     

Inducible synthesis of β-galactosidase inKluyveromyces fragilis

Lactose,d-galactose, andl-arabinose induce the synthesis of β-galactosidase inKluyveromyces fragilis. Lactose is the best inducer with a maximum effect at 1.4 mm. The induced synthesis of the enzyme in glycerol grown stationary phase cells is triggered within 30 min of inducer addition, the full induction being achieved within subsequent 30–40 min.     

A convenient synthesis of 5′-deoxyribonucleosides

A facile, two-step synthesis has been devised for the chemical preparation of 5′-deoxyribonucleosides from the parent nucleosides via the 5′-chloro-5′-deoxy-nucleosides. Treatment of 5′-chloro-5′-deoxynucleosides with tributyltin hydride and α,α′-azobis(isobutyronitrile) in dry tetrahydrofuran yields the corresponding 5′-deoxy-nucleosides. Dechlorination of 5′-chloro-5′-deoxythymidine with tributyltin hydride gives 1-(2,5-dideoxy-β-D-erythro-pentofuranosyl)thymine (5′-deoxythymidine) in good yield. Similarly, dechlorination of 9-(3,5-dichloro-2,3,5-trideoxy-β-D-threo-pentofuranosyl)adenine and 1-(3,5-dichloro-2,3,5-trideoxy-β-D-threo-pentofuranosyl)thymine yields the corresponding two trideoxynucleosides.     

Glycosidase-catalysed synthesis of glycosylated amino acids: synthesis of GalNAcα-Ser and GlcNAcβ-Ser derivatives

A glycosidase from Aspergillus oryzae catalysed the stereospecific formation of various derivatives of the Tn antigen, D-GalNAca1O-L-Ser, employing D-GalNAc-OPhNO - p as glycosyl donor and different N- and C-protected L-Ser derivatives as acceptors. The same glycosidase preparation was also useful for stereospecific preparation of D-GalNAca1O-L-Thr and D-GlcNAc1O-L-Ser derivatives. Yields were in the range 10-50% depending on the type of acceptor. Lipase from porcine pancreas was used for specific hydrolysis, generating a Tn antigen derivative with a free carboxyl group. This facilitates the use of the derivatives in e.g. solid phase synthesis of glycopeptides.     

High-yield enzymatic synthesis of O-allyl β-d-galactopyranoside

A high-yield synthesis of O-allyl β-d-galactopyranoside was carried out by the use of Aspergillus oryzae β-galactosidase. The reaction was carried out employing p-nitrophenyl β-d-galactopyranoside as the donor and a large excess of allyl alcohol as the acceptor. The molar yield was 65.6%, corresponding to an improvement of 41.3% with respect to the best results previously reported with other systems, and of 80.2% with respect to the results obtained using the same enzyme.     

Is there proofreading during polypeptide synthesis?

The stoichiometric efficiency with which ternary complexes containing Phe-tRNAphe and Leu-tRNAleu support polypeptide synthesis has been compared in a poly(U)-directed, steady-state translation system. When unfractionated tRNA is used to support synthesis, the number of discharged ternary complexes per peptide bond formed is an average of 48 times greater for leucine than for phenylalanine. When three purified leucine isoacceptor species are tested, they each show a characteristic ratio of ternary complexes discharged per missense insertion, normalized to that for phenylalanine: these are 103, 76, and 45 for Leu- tRNA2leu , Leu- tRNA3leu , and Leu- tRNA4leu , respectively. The data are consistent with the functioning of a proofreading mechanism during translation.     

Facile synthesis of 2′-substituted lactoses

Isopropylidenation of lactose with 2,2-dimethoxypropane in the presence ofp-toluenesulfonic acid gave two products, which were identified by¹H- and¹³C-NMR as 2,35,63,4-tri-O-isopropylidenelactose dimethyl acetal (1) and its 6-O-(2-methoxy)-isopropyl derivative (2). These products were used for the synthesis of 2-O-methyllactose (7), 2,6-di-O-methyllactose (9) and 2-O-benzyllactose (13).     

A diastereoselective synthesis of 7α-nitromethyl steroid derivative and its use for an efficient synthesis of eplerenone

A novel and efficient method of stereoselectively introducing α-nitromethyl group to C-7 position of 11α-hydroxyl canrenone 4 was described. In addition, this method was successfully applied in a total synthesis of Eplerenone 8. The route was characteristic of simple operation, moderate reaction conditions with 5 steps and 55% total yield, at the same time, without any expensive or toxic reagent in use.     

Interaction between membrane properties and protein synthesis in reticulocytes — A two step inhibition of protein synthesis by Valinomycin

In this work we consider the differential effect of Valinomycin used at different concentrations both on the protein synthesis of reticulocytes and on 42K exchange. We demonstrate that there is a two step action of this antibiotic. At 10(-6)M and below the drug has no effect on the 42K exchange, but it stops, however reversibly, protein synthesis. At 10(-5)M the drug has a very sharp action on the 42K exchange and stops protein synthesis in an irreversible way. Ribosomal population checked by two ways, sucrose gradient and direct counting on E.M. sections shows that at low concentrations of Valinomycin (10(-8)M to 10(-6)M) there is no breakdown of the polysomes which can be detected by either one of these methods. On the contrary, after short incubation with 10(-5)M of Valinomycin the breakdown of ribosomes is very clear, as evidenced by sucrose gradient analysis. By direct ribosomes clusters counting on E.M. sections this breakdown is seen only after long incubation.     

Method for the synthesis of phosphinic acids from hypophosphites V. The synthesis of pseudo-α,α-dipeptides

Summary. Neurolathyrisim is a motor neuron disease characterized by spastic paraparesis in the hind legs, and is caused by grass pea, Lathyrus sativus, which contains the excitotoxic amino acid, 3-N-oxalyl-L-2,3-diaminopropanoic acid (L--ODAP), an -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamatergic receptor agonist. In an attempt to make a useful model of this disease, the CNS distribution and toxicity of L--ODAP was studied in rat neonates after parenteral administration. L--ODAP was detected in the spinal cord as well as in the pons/medulla oblongata, though only small amounts in the latter. Repeated injection of L--ODAP resulted in rats with paraparesis of the legs, though at a low incidence rate of 0.032. These paralyzed rats displayed the severe atrophy of the ventral root of the lumbar cord as well as degenerations of motor neuron. The rats were useful models for the study of motor neuron degeneration in the spinal cord.     

Chemoenzymatic synthesis of 1-deaza-pyridoxal 5′-phosphate

The first synthesis of 1-deaza-pyridoxal 5′-phosphate (2-formyl-3-hydroxy-4-methylbenzyl phosphate) is described. The chemoenzymatic approach described here is a reliable route to this important isosteric pyridoxal phosphate analogue. This work enables elucidation of the role of the pyridine nitrogen in pyridoxal 5′-phosphate dependent enzymes.     

A novel synthesis of 2-deoxy-α-glycosides

The key step of the synthesis involves the reaction of glycals [3,4,6-tri-O-acetyl-d-glucal (1), the new glycal derivative 4-O-acetyl-1,5-anhydro-2,6-dideoxy-3-C-methyl-3-O-methyl-l-ribo-hex-l-enitol (2), and 3-acetamido-4,6,-di-O-acetyl-1,5-anhydro-2,3-dideoxy-d-arabino-hex-l-enitol (3)] with 1.5 molar equivalents of several alcohols in the presence ofN-bromosuccinimide in acetonitrile to give mainly the corresponding 2-bromo-2-deoxy-α-glycopyranosides (4-21). The glycopyranosides (4-8 and16-21) from1 and3 have the α-d-manno configuration and those (10-15) from2 have the α-l-altro configuration. The yields are high from1, virtually quantitative from2, and moderate from3. Debromination of the 2-bromo-2-deoxy compounds with tributylstannane and a radical initiator gives the corresponding 2-deoxy-α-glycopyranosides (22-38) in quantitative yields. In particular, the branched-chain glycal2 reacts with alcohols to give exclusively the corresponding α-glycopyranosides (27-32) of cladinose in strikingly high overall yields. The stereoselectivity and regiospecificity of the bromination reaction are described. 1,3-Dibromo-5,5-dimethylhydantoin andN-bromoacetamide are also found to be useful for the reaction.