Practical synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine

Three synthetic methods for the preparation of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate in the synthesis of the novel quinolone antitumor agent, AG-7352, have been developed. By one route, an efficient and large-scale preparation of the chiral pyrrolidine could be achieved through resolution of (±)-1-Boc-3-benzylamino-4-hydroxypyrrolidine, which is prepared from either 3-pyrroline or 1,4-dichloro-2-butene.     

Efficient stereospecific synthesis of (S,S)-3-methoxy-4-methylaminopyrrolidine

Efficient stereospecific synthesis of (S,S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate for a novel quinolone antitumor agent AG-7352 is presented. Starting from either d- or l-tartaric acid, a stereospecific synthesis of the chiral pyrrolidine was achieved via two S_N2 displacement reactions. From the results of this synthetic study, the absolute structure of AG-7352 was chemically determined.     

Chemoenzymatic synthesis of (3S,4S)- and (3R,4R)-3-methoxy-4-methylaminopyrrolidine

Facile chemoenzymatic enantioselective synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, a key intermediate for a new quinolone antitumor compound AG-7352 has been described. This methodology illustrates the preparation of 3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine starting from diallylamine via 1-benzyloxycarbonyl-3-pyrroline obtained by ring-closing metathesis (RCM) employing Grubbs’ catalyst. Enzymatic transesterification employing PS-C lipase gave (3S,4S)-3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine in >99% ee, which upon methylation of the hydroxyl group followed by sequential reactions gave the desired intermediates, (3S,4S)-1-tert-butoxycarbonyl-3-tert-butoxycarbonylamino-4-methoxypyrrolidine.     

Stereoselective synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine

An efficient stereoselective approach for the synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine, a part of the structure of quinoline antibacterial compound (1a) and the naphthyridine antitumour agent (1b) has been described.     

Chemoenzymatic Synthesis of (R)- and (S)-4-Amino-3-Methylbutanoic Acids

(R)- and (S)-4-Amino-3-methylbutanoic acids were synthesized in high yields via initial enantioselective hydrolysis of dimethyl 3-methylglutarate to methyl (R)-3-methylglutarate with pig liver esterase. The ester group was converted to an amine to give (R)-4-amino-3-methylbutanoic acid; the carboxylic acid was converted to an amine to give (S)-4-amino-3-methylbutanoic acid.     

Total synthesis of (3R, 4S)-4-hydroxylasiodiplodin

Abstract

An alternative and concise total synthesis of (3?R, 4S)-4-Hydroxylasiodiplodin has been reported from inexpensive and commercially available 6-heptenal and Orsellinic acid starting materials. The key steps involved in the synthesis are Wittig reaction, Sharpless epoxidation, Yamaguchi esterification and ring-closing metathesis (RCM).     

光学纯（4S，5R）－4－甲基－5－羟基－3－羰基己酸特丁酯的化学酶促合成

采用化学方法合成了4－甲基－3，5－二羰基己酸特丁酯。以Lactobacillus brevis醇脱氢醇为生物催化剂，选择性地将4－甲基－3，5－二羰基己酸特丁酯还 原为（4S，5R）－4－甲基－5－羟基－3－羰基己酸特丁酯（99．2％ ce,sym: anti=97:3)。     

Convenient synthesis of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4- chlorophenyl）-6-（hydroxymethyl）-tetrahydro- 2H-pyran-3,4,5-triol

A convenient approach for the preparation of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4-chlorophenyl）-6-（hydroxymethyl）- tetrahydro-2H-pyran-3,4,5-triol I is developed. The target compound via four steps is synthesized from 4-bromo-2-（bromomethyl）- 1-chlorobenzene and the isomers of undesired ortho-products were avoided during the preparation.     

Practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid

A practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid was accomplished via an unconventional Evans anti-aldol reaction followed by a one-pot azide reduction/reductive cyclization.     

Stereoselective synthesis of (2R,3S,4S,5R)-trans-3,4-dihydroxy-5-(4-fluorophenoxymethyl)-2-(1-N-hydroxyureidyl-3-butyn-4-yl)tetrahydrofuran and (2R,3S,4S,5R)-trans-5-ethynyl-2-(4-fluorophenoxymethyl)-3,4-O-isopropylidene tetrahydrofuran from mannose diacetonide

Stereoselective synthesis of pharmaceutically interesting chiral tetrahydrofurans starting from mannose diacetonide is reported. A 1,4-diol system derived from mannose diacetonide, through a Mitsunobu reaction was stereospecifically cyclized to give chiral tetrahydrofurans. Both the C-1 and C-4 centers of d-mannose are successfully exploited to install the requisite side chains.     

Asymmetric synthesis of (1R,2S,3R)-2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)thiazole

Two different methods for preparing the thiazole analogue 3 of the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4- tetrahydroxybutyl)imidazole 1 are reported.     

Chemoenzymatic preparation of (2S,3S)- and (2R,3R)-2,3-butanediols and their esters from mixtures of d,l- and meso-diols

An efficient method of preparing the pure enantiomers of 2,3-butanediol from commercially available mixtures of the d,l- and meso-isomers was developed. It furnished (2S,3S)-2,3-butanediol with >99% e.e. and a >99.5/0.5 diastereomeric ratio and (2R,3R)-2,3-butanediol in 95% e.e. and >95/<5 diastereomeric ratio.     

Asymmetric synthesis of (2S,3R,4R)-ethoxycarbonylcyclopropyl phosphonoglycine

The synthesis of enantiomerically pure (2S,3R,4R)-ethoxycarbonylcyclopropyl phosphonoglycine is described, the key-step involving 1,4-addition of a chiral enolate to ethyl 4-bromo-crotonate.     

Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate

Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective epimerisation of tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate by treatment with KO'Bu in 'BuOH gives tert-butyl (1S,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate in quantitative yield and in > 98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving (1S,2S,3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.     

Chemoenzymatic asymmetric total syntheses of antitumor agents (3R,9R,10R)- and (3S,9R,10R)-Panaxytriol and (R)- and (S)-Falcarinol from Panax ginseng using an enantioconvergent enzyme-triggered cascade reaction

Total asymmetric synthesis of two components of Panax ginseng showing antitumor activity, i.e., (3R,9R,10R)- and (3S,9R,10R)-Panaxytriol and of both enantiomers of Falcarinol was accomplished. Due to the fact that the synthetic strategy was based on enantioconvergent biotransformations, the occurrence of any undesired stereoisomer was entirely avoided. The absolute configuration of naturally occurring Panaxytriol was confirmed to be (3R,9R,10R) on the basis of optical rotation values. It was shown that enzyme-triggered cascade reactions represent a valuable tool for the synthesis of natural products.     

Enantioselective synthesis of (2R,3R)- and (2S,3S)-2- [(3-chlorophenyl)-(2-methoxyphenoxy)methyl]morpholine

The enantioselective synthesis of the (R,R)- and (S,S)-enantiomers of 1 from commercially available 3-chlorocinnamic acid is reported. The Sharpless asymmetric epoxidation was used to establish the stereocenters in the synthesis of both enantiomers of 1.     

Asymmetric syntheses of (1r,3R,4S)- and (1s,3R,4S)-(3,4-difluorocyclopentyl)-alanine derivatives

By employing a sequence of epoxide opening, asymmetric alkylation, and fluorination, polyfluorinated cyclopentylamino acids with defined stereochemistries were prepared.