Enantioselective synthesis of (S)-N,N-diethyl-2-formyl-2-(methoxymethoxy)butyramide,a key intermediate for 20(S)-camptothecin analogues,via asymmetric bromolactonization

A new enantioselective synthetic method for enantiomerically pure (S)-N,N-diethyl-2-formyl-2-(methoxymethoxy)butyramide 5, a versatile key intermediate has been developed employing asymmetric bromolactonization using (S)-proline as the chiral auxiliary.     

Azabicyclo[3.1.0]hexane-1-ols as frameworks for the asymmetric synthesis of biologically active compounds

Azabicyclo[3.1.0]hexane-1-ols, easily obtained by Ti(IV)-mediated cyclopropanation of amino acid derivatives, constitute versatile, and unprecedented intermediates for the asymmetric synthesis of pharmacologically active products. Indeed, through selective rearrangement, these compounds undergo unusual ring cleavage to lead to pyrrolidinones. Fe(III)-promoted ring opening followed by basic dehydrohalogenation furnishes optically active dihydropyridinones, while Ce(IV)-promoted ring opening provides chiral tricyclopiperidinones via a radical process.     

Selective methodologies for the synthesis of biologically active piperidinic compounds

The synthesis of optically active substituted piperidines has been achieved by using four different methodologies. The first one is an intramolecular nucleophilic displacement of activated alcohol moieties that was used to build up the piperidine ring of (-)-prosophylline and (-)-slaframine, and the second one is a ring-closing metathesis of unsaturated amines which was employed in the synthesis of (+)-sedamine and 4a,5-dihydrostreptazoline. The third methodology is the alpha-functionalization of N-Boc piperidines which was particularly useful in the synthesis of argatroban, and the fourth one is a ring expansion of prolinols to 3-chloropiperidines or 3-hydroxypiperidines which was utilized to synthesize (-)-paroxetine, (-)-pseudoconhydrine, the piperidine ring of (-)-velbanamine and (+)-zamifenacin.     

Chemoenzymatic synthesis of (S)-2-cyanopiperidine,a key intermediate in the route to (S)-pipecolic acid and 2-substituted piperidine alkaloids

The preparation of (S)-2-cyanopiperidine 4 provides a new access to 2-substituted piperidines. This synthesis is based on an enantioselective (R)-oxynitrilase-catalyzed reaction for the preparation of (R)-(+)-6-bromo-2-hydroxyhexanenitrile 1 and the subsequent cyclization of this compound to yield the piperidine ring. The utilization of 4 as the starting material for the synthesis of (S)-2-aminomethylpiperidine 6, (R)-(−)-coniine 10 and (S)-(−)-pipecolic acid 13 is also described.     

Water-soluble poly(n-vinylamides)as a basis for the synthesis of polymeric carriers of biologically active compounds

The method for preparation of copolymers of N-vinylpyrrolidone (VP) and N-vinylamine (VA) with high yield were developed; the method involves radical copolymerization of VP with N-vinylformamide(VFA) followed by the removal of formyl protecting group in the presence of inorganic acids. The optimal conditions for synthesis of copolymers with predefined compositions and molecular masses were determined. The influence of temperature, concentrations of reactants, and the nature of an acid on the rate of formyl group removal was estimated. Spectral and chromatographic methods of analytical control of the contents of residual monomers and formic acid (which forms during acidic hydrolysis of the copolymer) were developed.     

Simple synthesis of 2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene,a key intermediate for the synthesis of optically active anthracycliones

2-Acetyl-5,8-dimethoxy-3,4-dihydronaphthalene is synthesised easily·starting from 2-acetyl-5,8-dimethoxytetralone.     

Preparative resolution of a key intermediate for the synthesis of optically active m-phenylene PGI2 derivatives

A key intermediate for the synthesis of optically active m-phenylene PGI₂ derivatives was efficiently resolved on a preparative scale by diastereomeric salt formation method using (+)-cis-N-benzyl-2-(hydroxymethyl)cyclohexylamine ((+)-cis-amine) as a resolving agent.     

具生物活性有机磷化合物的设计与合成

对氨基膦酸及磷肽的合成作了研究,同时考察了引入二氟次甲基及三氟甲基的方法。在此基础上研究成功基于[1,2]不对称诱导及[1,3]质子转移反应的手性合成方法。对多官能团的氨基膦酸及磷肽也作了研究。此外还制备了具1,1-双膦酸基的多种碳环化合物,对含磷酰基,特别对既含磷酰基又含三氟甲基的多种杂环化合物的合成方法与反应机理进行了报导。     

不对称羟内酯化合成白三烯A4中间体

为合成白三烯A4的关键中间体, 本文试验了若干7-手性中心-6,5-双键庚酸衍生物的不对称环氧化方法, 发现从D-甘油醛得的顺式烯化合物可选择性地羟内酯化, 游离羟基甲磺酰化后甲醇纳处理可得所需的5S, 6R氧桥, 水解, 过碘酸钠断键后即可顺利得到目标化合物.     

Expedient synthesis of substituted (S)-N-(alpha-methylbenzyl)aziridines

We report for the first time that after O-acylation the conjugate addition products of (S)-N-(alpha-methylbenzyl)hydroxylamine undergo an efficient diastereoselective 3-exo-tet ring-closure reaction affording 2- and 2,3-disubstituted-N-alkylaziridines in good to excellent yields.     

A practical procedure for the large-scale preparation of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate,a key intermediate for diltiazem

A practical synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), was developed. Treatment of methyl (E)-4-methoxycinnamate 3 with chiral dioxirane, generated from chiral ketone 4, provided (-)-2 in 77% ee and 89% yield. The crude mixture of (-)-2 and 4 was efficiently separated by the use of novel and simple equipment performing a lipase-catalyzed transesterification and a continuous dissolution and crystallization to furnish the optically pure (-)-2 and recovery of 4 in 74% and 91% yield, respectively.     

A new asymmetric synthesis of (2S,3R,4R,5S)-trihydroxypipecolic acid

A novel four step synthesis of enantiomerically pure (2S,3R,4R,5S)-trihydroxypipecolic acid, starting from readily available materials, that is, condensation products of (R)-(−)-phenylglycinol with a mesotrihydroxylated glutaraldehyde, is described. The scope and limitations of the reaction have also been investigated.     

Search for biologically active substances among heteroaromatic compounds (review)

Research on the synthesis and investigation of the chemical and spectral characteristics of heterocyclic compounds carried out in the department of chemistry Osmania University (Hyderabad, Andra Pradesh, India) is examined in the review.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 291–310, March, 1977.     

The Grandberg reaction in the synthesis of biologically active compounds

The review is focused on the Grandberg synthesis, namely, the synthesis of tryptamines from arylhydrazines and γ-halocarbonyl compounds, as an exceptionally useful and efficient methodology to access biologically active indole heterocycles.     

A new enzymatic strategy for the preparation of (2R,3S)-3-phenylisoserine: a key intermediate for the Taxol side chain

Burkholderia cepacia lipase PS-IM catalysed the hydrolysis of racemic ethyl 3-amino-3-phenyl-2-hydroxypropionate with excellent enantioselectivity (E >200), when the reaction was performed with added H₂O as a nucleophile, in iPr₂O, at 50 °C. The hydrolysis of the less reactive enantiomeric ethyl 3-amino-3-phenyl-2-hydroxypropionate with 18% HCl afforded the corresponding enantiomerically pure (2R,3S)-3-amino-3-phenyl-2-hydroxypropionic acid hydrochloride, a key intermediate for the Taxol side chain.     

Asymmetric synthesis of optically pure (R)(−)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol,a key intermediate for optically active anthracyclinone synthesis

Asymmetric reduction of 2-acetyl-5,8-dimethoxy-3,4-dihydronaphthalene(3) with lithium aluminum hydride partially decomposed with (?)-N-methylephedrine and N-ethylaniline was found to give the optically active allylic alcohol((?)-4) in 92% optical yield. Optically pure (?)-4 obtained in 87% yield based on 3 by recrystallization, was elaborated to the title compound((R)(?)-1) according to the reaction scheme exploited in the preceding paper.     

Highly enantioselective synthesis of terutroban key intermediate via asymmetric hydrogenation

A chiral (R) key intermediate of the biologically active form of terutroban has been prepared by asymmetric hydrogenation. The catalysts are based on very easily accessible ruthenium complexes modified by chiral phosphorous ligands. The use of the chiral catASium^®T ligands family allowed us to realize this transformation efficiently in terms of yield and enantioselectivity (ee up to 92%) with high substrate/catalyst ratios.