Convenient Synthesis of 3-(S)-Amino-γ-butyrolactone

Abstract

An efficient two step conversion of N-t-Boc-L-aspartic acid b-benzyl ester to enantiopure 3-(S)-amino-g-butyrolactone is described. In this route, chemoselective reduction of the a-carboxylic group in the starting material via a mixed anhydride with NaBH 4 afforded the corresponding alcohol in 95% yield without any loss of the optical purity. Subsequent acidic hydrolysis of the Nprotected b-amino alcohol not only deprotected the amino group, but also produced the desired g-lactone in 98% yield with complete retention of the optical activity.

Preparative synthesis of β-amino alcohols from α-amino dicarboxylic acid derivatives

“…Their purity was evaluated by measuring their melting points which in all cases coincided with published data. The enantiomeric purity of amino alcohols IIa and IIb was determined from the optical rotation values which coincided with the data reported for analogous compounds prepared by reduction with borane in THF [7,11].…”

“…β-Amino alcohols are also used as starting compounds in the synthesis of such chemically important intermediate products as α,α′-diamino dicarboxylic acids [6], (3S)-amino-γ-butyrolactone [7], (S)-γ-fluoroleucine [8], and various β-amino acids through β-iodo amines [9].…”

Synthesis and Reactivity of 2-(Carboxymethyl)aziridine Derivatives

“…Subsequently, a Mitsunobu reaction with DIAD took place which gave the corresponding N -Boc 2-(carboxymethyl)­aziridines 133a – c in good yields (63–73%). It is noteworthy that treatment of compound 132a with a saturated hydrochloric acid solution in diethyl ether resulted in formation of the ( S )-3-amino-γ-butyrolactone 11 , which is a constitutional isomer of the 2-(aziridinyl)­acetic acid 1 (vide supra) …”

Stabilization of NaBH4 in Methanol Using a Catalytic Amount of NaOMe. Reduction of Esters and Lactones at Room Temperature without Solvent-Induced Loss of Hydride

“…Carrying out the reduction of esters using sodium borohydride at room temperature would be highly desirable since NaBH 4 is extensively used in chemical industry . NaBH 4 easily reduces aldehydes and ketones to the corresponding alcohols. − It also reduces electrophilic carbonyls like ketoesters, anhydrides, , acid chlorides, and imides . Reduction of carbonyl groups that are less reactive than these highly reactive systems is always a major challenge when carbonyls with different electron demands are present in a substrate.…”