Synthesis of the cis and trans isomers of 4-Chloro-L-proline, 4-Bromo-L-proline, and 4-Amino-L-proline

Abstract

cis- and trans-4-Chloro- and 4-bromo-L-prolines have been synthesized stereospecifically, the key step being SN2 displacement of a free or substituted 4-hydroxyl group in suitably protected 4-hydroxy-L- prolines. Similar displacements with azide ion followed by reduction provide convenient routes to cis- and trans- 4-amino-L-proline. A less satisfactory pathway to cis-4-aminoproline is reduction of a 4- oximinoproline derivative. In the course of the syntheses, which involve a variety of protecting groups, 45 new L-proline derivatives have been prepared. Unexpected side reactions were the formation of cis-4-hydroxyprolinamide by the action of ammonia on trans-4- bromoproline, and the reduction by sodium borohydride of N- benzyloxycarbonyl-4-oximinoproline methyl ester to N-benzyloxycar- bonyl-4-oximinoprolinol.

Relationships between the stereochemistry and biological activity of fungal phytotoxins

“…14). Although the trans-4-aminoprolines are well known as synthetic compounds, 146,147 this represents the first isolation of the (1)-trans-4-D-aminoproline as a naturally occurring compound and as a phytotoxin produced by A. caulina.…”

Spin labeled hydroxyproline analogues

“…The (2S,4R) configuration of 3 was established by X-ray diffraction [12]. Upon treatment with Nmethylhydroxylamine hydrochloride, the ketone 6 [11] afforded an E/Z mixture of the unstable nitrone 7 which was directly reduced (NaBH 3 CN) to a 2:1 mixture (94% from 6) of 8 and 9 from which only 8 could be isolated in a pure state. From the acetylated mixture of 8 and 9, the major isomer 10 (49%) was obtained by recrystallization.…”

“…Upon cyanoborohydride reduction, oxime 1 [11] led to a 2:1 mixture (83%) of 2 and 3 from which only 2 could be obtained in pure state by crystallization (Scheme 1). The diastereoisomeric mixture of 2 and 3 was submitted to O-silylation and a chromatographic separation of the O-silyl derivatives afforded pure 4 (39%) and 5 (15%).…”

A New Enantioselective Approach to Total Synthesis of the Securinega Alkaloids: Application to (−)-Norsecurinine and Phyllanthine

“…It had been shown that U III complexes would act as one-electron reductants with cyclooctatetraene. [10] Our efforts to couple that reactivity with sterically induced reduction are reported here.…”

“…The enantiomerically pure ester 9, prepared from trans-4-hydroxy-l-proline (8), [10] was converted via the a,b-unsaturated nitrile 10 to ketonitrile 11 (Scheme 2). We were pleased to find that exposure of 11 to SmI 2 , followed by acidic hydrolysis, provided the key scalemic bicyclic BC-ring system 12 in good yield.…”