Conversion of L-pyroglutamic acid to 4-alkyl-substituted L-prolines. The synthesis of trans-4-cyclohexyl-L-proline

Abstract

5-(Hydroxymethyl)-2-pyrrolidmone (3), prepared from L-pyroglutamic acid, was condensed with benzaldehyde to obtain the 0,iV-acetal 4 in excellent yield. Alkylation of 4 with 3-bromocyclohexene followed by reduction gave ímras-4-cyclohexyl-L-prolmol (7) in good chemical yield with excellent stereoselectivity. Sequential N-protection, oxidation of the alcohol to the acid, and N-deprotection furnished trons-4-cyclohexyl-L-proline (1) in excellent yield and quality. Compound 1 serves as an intermediate for the preparation of ACE inhibitors including Fosenopril.

Diastereospecific synthesis of (S,S)‐2‐substituted‐4,4‐diphenyl‐3, 1‐oxazabicyclo[3.3.0]octanes

“…The development of the methodology for the preparation of highly functionalized pyrrolidines has attracted considerable interest recently [1][2][3][4]. The trans bicyclic derivatives of pyrrolidine, trans-3,1-oxazabicyclo [3.3.0]octan-8-one derivatives, can be synthesized mainly from aldehydes and related chiral hydroxymethylpyrrolidinones, which are derived from L-pyroglutamic acid [1][2][3][4]13]. Herein we report the preparation of cis bicyclic derivatives of pyrrolidine, chiral cis-3,1-oxazabicyclo[3.3.0]octanes, from aldehydes and (S)-2-(hydroxydiphenylmethyl)pyrrolidine, which was obtained from L-proline.…”

Synthesis of Bioactive 2‐Aza‐Analogues of Ipecac and Alangium Alkaloids

“…(3S,11 bR)-3-Ethyl-9,10-dimethoxy-1,3,4,6,7,11 b-hexahydro-2H-pyrazino[2,1-a]isoquinoline (6) The secondary amine 11 (2.0 g, 6.9 mmol) was dissolved in dry THF (15 mL) and LiAlH 4 (2 m in THF, 17 mL, 34.5 mmol, 5 equiv) was added. [40] The grey suspension was stirred for 2 h at 50 8C. After cooling to RT, the reaction was quenched by the addition of 2 n aq NaOH (10 mL) at 0 8C, and the colorless precipitate (insoluble aluminum salts) was removed by filtration.…”

4,4′‐Disubstituted L‐Prolines as Highly Enantioselective Catalysts for Direct Aldol Reactions

“…The disubstituted lactams 4a-d and 4f-g were prepared from l-glutamic acid according to the reported procedure. [15,16] Scheme 1 depicts the sequence for the synthesis of proline derivatives 1a-d and 1f-h. Thus, double alkylation of 2 with alkyl halide followed by sequential deprotection, reduction, N-protection, oxidation of the alcohol and hydrogena- …”