Enantioselective total syntheses of [6R,7R] and [6S,7S] tricyclic beta-lactams

被引:49
作者
Niu, CS [1 ]
Pettersson, T [1 ]
Miller, MJ [1 ]
机构
[1] UNIV NOTRE DAME,DEPT CHEM & BIOCHEM,NOTRE DAME,IN 46556
关键词
D O I
10.1021/jo951651u
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The reaction of Ox-glycyl chloride with a chiral imine derived from the combination of D-(R)-glyceraldehyde acetonide and protected D-threonine afforded optically active, highly functionalized cis-substituted beta-lactams 11 and 12. These beta-lactams provide versatile intermediates for the syntheses of biologically important carbacephalosporins, isooxacephems, and other multicyclic beta-lactams. Desilylation and oxidation of 12 with Dess-Martin periodinane followed by intramolecular cyclization produced a novel tricyclic beta-lactam 17 and a 1-(hydroxymethyl)-O-2-isocephem 18 with [6R,7R] absolute configuration. Removal of the Ox protecting group and acylation of 17 in a one-pot reaction followed by saponification furnished the target salt 24. Alternatively, reaction of phthaloylglycyl chloride with the chiral imine derived from the combination of L-(S)-glyceraldehyde acetonide and protected D-threonine gave only one enantiomeric azetidinone 27 in high yield. Further manipulation of 27 provided a new tricyclic beta-lactam 39 with [6S,7S] absolute configuration which satisfies the stereochemistry typically required for antibacterial activity, This synthetic procedure provides a short, versatile and enantioselective method of preparing polycyclic beta-lactams. Biological testing of these tricyclic beta-lactams indicated that salt 39 has potential inhibitory activity against four typical strains of bacteria.
引用
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页码:1014 / 1022
页数:9
相关论文
共 90 条
[61]   CARBON-CARBON BOND FORMATION AT THE C-4 POSITION OF AN AZETIDIN-2-ONE RING BY INTERMOLECULAR RADICAL COUPLING REACTIONS - A ROUTE TO TRIBACTAMS [J].
PADOVA, A ;
ROBERTS, SM ;
DONATI, D ;
PERBONI, A ;
ROSSI, T .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1994, (04) :441-442
[62]   PREPARATION OF CHIRAL 3-UNSUBSTITUTED BETA-LACTAMS FROM 3-HYDROXY BETA-LACTAMS BY USING THE ALKOXYKETENE-IMINE CYCLOADDITION REACTION AS AN APPROACH TO THE AZETIDINONE RING - A FORMAL SYNTHESIS OF THE CARBAPENEM ANTIBIOTIC (+)-PS-5 [J].
PALOMO, C ;
COSSIO, FP ;
ONTORIA, JM ;
ODRIOZOLA, JM .
TETRAHEDRON LETTERS, 1991, 32 (26) :3105-3108
[63]  
PASTO DJ, 1992, EXPT TECHNIQUES ORGA, P504
[64]   SYNTHESIS OF NOVEL FUSED BETA-LACTAMS BY INTRAMOLECULAR 1,3-DIPOLAR CYCLO-ADDITIONS .2. (8S,8AR)-7,8-DIHYDRO-7-OXO-8-PHENOXYACETAMIDO-8AH-AZETO[1,2-A]-V-TRIAZOLO[3,4-C]PYRIMIDINE-5-CARBOXYLIC ACIDS [J].
PEARSON, MJ .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1981, (09) :2544-2551
[65]  
PERRIN DD, 1980, PURIFICATION LABORAT
[66]   STEREOSELECTIVE FORMATION OF TRICYCLIC CEPHALOSPORINS IN REACTIONS OF CEPHEM PHOSPHORUS YLIDES AND KETOALDEHYDES [J].
PITLIK, J ;
GUNDA, TE ;
BATTA, G ;
JEKO, J .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (11) :2451-2456
[67]   TOTAL SYNTHESES OF (-)-NOCARDICINS A-G - A BIOGENETIC APPROACH [J].
SALITURO, GM ;
TOWNSEND, CA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (02) :760-770
[68]   SYNTHESIS OF 2,3-O-ISOPROPYLIDENE-D-GLYCERALDEHYDE IN HIGH CHEMICAL AND OPTICAL PURITY - OBSERVATIONS ON THE DEVELOPMENT OF A PRACTICAL BULK PROCESS [J].
SCHMID, CR ;
BRYANT, JD ;
DOWLATZEDAH, M ;
PHILLIPS, JL ;
PRATHER, DE ;
SCHANTZ, RD ;
SEAR, NL ;
VIANCO, CS .
JOURNAL OF ORGANIC CHEMISTRY, 1991, 56 (12) :4056-4058
[69]   SYNTHESIS AND BIOLOGICAL-ACTIVITY OF TETRACYCLIC CARBAPENEMS [J].
SCHMIDT, G ;
SCHROCK, W ;
ENDERMANN, R .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (11) :2193-2198
[70]   STUDIES OF THE FURAN-CARBONYL PHOTOCYCLOADDITION REACTION - THE DETERMINATION OF THE ABSOLUTE STEREOSTRUCTURE OF ASTELTOXIN [J].
SCHREIBER, SL ;
SATAKE, K .
TETRAHEDRON LETTERS, 1986, 27 (23) :2575-2578