Chemoenzymatic Synthesis of α-Hydroxy-β-methyl-γ-hydroxy Esters: Role of the Keto-Enol Equilibrium To Control the Stereoselective Hydrogenation in a Key Step

被引:15
作者
Milagre, Cintia D. F. [1 ]
Milagre, Humberto M. S. [2 ]
Moran, Paulo J. S. [1 ]
Rodrigues, J. Augusto R. [1 ]
机构
[1] Univ Estadual Campinas, Inst Chem, BR-13084970 Campinas, SP, Brazil
[2] UNESP, Inst Biosci, BR-13506900 Rio Claro, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
SELECTIVE ASYMMETRIC HYDROGENATION; ENANTIOSELECTIVE REACTIONS; ETHYL-BENZOYLACETATE; ENOATE REDUCTASES; BAKERS-YEAST; BIOREDUCTION; REDUCTION; ACIDS; SOLVENT; NIKKOMYCINS;
D O I
10.1021/jo902227f
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
alpha-Hydroxy-beta-methyl-gamma-hydroxy esters not only are found in many natural products and potent drugs but also are useful intermediates in organic synthesis due to their highly functionalized skeleton that can be further manipulated and applied in the synthesis of many compound with remarkable biological activities. This work was based on a chemoenzymatic approach to obtain these molecules with three contiguous stereogenic centers in a highly enantio- and diastereoselective way. Two distinct linear routes were proposed in which the key steps in both routes consisted of initial stereocontrolled ketoester bioreduction followed by unsaturated carbonyl bioreduction or reduction with Pd-C. Other key reactions in the synthesis include a Wasserman protocol for chain homologation and a Mannnich-type olefination with maintenance of enantiomeric excess for all intermediates during the sequence. Whereas route A gave exclusively the skeleton with 3R,4R,5S configuration (99% ee and 11.5% global yield after 7 steps), route B gave the skeleton with 3R,4R,5S and 3R,4S,5R configurations (dr 1:12, 98% ee and 20% global yield after 5 steps).
引用
收藏
页码:1410 / 1418
页数:9
相关论文
共 69 条
[31]   Direct Methods for Stereoselective Polypropionate Synthesis: A Survey [J].
Li, Jun ;
Menche, Dirk .
SYNTHESIS-STUTTGART, 2009, (14) :2293-2315
[32]   Effect of solvent and hydrogen during selective hydrogenation [J].
Maki, S ;
Harada, Y ;
Matsui, R ;
Okawa, M ;
Hirano, T ;
Niwa, H ;
Koizumi, M ;
Nishiki, Y ;
Furuta, T ;
Inoue, H ;
Iwakura, C .
TETRAHEDRON LETTERS, 2001, 42 (47) :8323-8327
[33]   Direct anti-selective asymmetric hydrogenation of α-amino-β-keto esters through dynamic kinetic resolution using Ru-axially chiral phosphine catalysts-stereoselective synthesis of anti-β-hydroxy-α-amino acids [J].
Makino, Kazuishi ;
Goto, Takayuki ;
Hiroki, Yasuhiro ;
Hamada, Yasumasa .
TETRAHEDRON-ASYMMETRY, 2008, 19 (24) :2816-2828
[34]  
MANZOCCHI A, 1987, J CHEM SOC P1, V12, P2753
[35]   Highly diastereo- and enantioselective reactions of enecarbamates with an aldehyde [J].
Matsubara, R ;
Vital, P ;
Nakamura, Y ;
Kiyohara, H ;
Kobayashi, S .
TETRAHEDRON, 2004, 60 (43) :9769-9784
[36]   Highly diastereo- and enantioselective reactions of enecarbamates with ethyl glyoxylate to give optically active syn and anti α-alkyl-β-hydroxy imines and ketones [J].
Matsubara, R ;
Nakamura, Y ;
Kobayashi, S .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (25) :3258-3260
[37]   Recent progress in biocatalysis for asymmetric oxidation and reduction [J].
Matsuda, Tomoko ;
Yamanaka, Rio ;
Nakamura, Kaoru .
TETRAHEDRON-ASYMMETRY, 2009, 20 (05) :513-557
[38]   New methods for stereochemical determination of complex polyketides: configurational assignment of novel metabolites from myxobacteria [J].
Menche, Dirk .
NATURAL PRODUCT REPORTS, 2008, 25 (05) :905-918
[39]   Probing the mechanism of direct Mannich-type α-methylenation of ketoesters via electrospray ionization mass spectrometry [J].
Milagre, Cintia D. F. ;
Milagre, Humberto M. S. ;
Santos, Leonardo S. ;
Lopes, Marcelo L. A. ;
Moran, Paulo J. S. ;
Eberlin, Marcos N. ;
Rodrigues, J. Augusto R. .
JOURNAL OF MASS SPECTROMETRY, 2007, 42 (10) :1287-1293
[40]   Screening and reaction engineering for the bioreduction of ethyl benzoylacetate and its analogues [J].
Milagre, Cintia D. F. ;
Milagre, Humberto M. S. ;
Moran, Paulo J. S. ;
Rodrigues, J. Augusto R. .
JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC, 2009, 56 (01) :55-60