Studies on cyclization reactions of 3-amino-2,4-dihydroxybutanoic acid derivatives

Abstract

A number of cyclic derivatives of 3-amino-2,4-dihydroxybutanoic acid are known in the literature but they are often prepared from other cyclic precursors. This study showed that the title compound too may serve as a convenient substrate for cyclization reactions. Using orthogonally-protected linear derivatives, regioselective cyclizations were performed, leading to original and highly-functionalized γ-lactones, oxazolidinones, oxazolines and aziridines. In these reactions a key role was played by the C3 nitrogen group function, while the C2 alcohol function showed no propensity for participation in cyclization reactions.

Reversal of Diastereoselectivity in a Masked Acyl Cyanide (MAC) Reaction: Synthesis of Protected erythro-β-Hydroxyaspartate Derivatives

“…The anti geometry of 17 was confirmed by X-ray crystallography (CCDC 1888028; Figure ). Both 16 and 17 were observed previously as side products in the studies of the syn -selective MAC reaction conducted on N -Boc- O -benzylserinal . In those studies, the syn diastereomer of 17 was transformed into a syn α-hydroxy-β-aziridino ester .…”

“…The α-hydroxy-β-amino acid moiety is thus constructed and derivatized (as an ester or an amide) in a one-pot procedure (Scheme a) . Since the nucleophile can be the free amine of an amino acid or a peptide, MAC reactions have been employed in the syntheses of the natural products bestatin and cyclotheonamide C, as well as α-ketoamide serine protease inhibitors and heterocycles derived from 3-amino-2,4-dihydroxybutanoic acid. , …”

“…protease inhibitors 13 and heterocycles derived from 3-amino-2,4-dihydroxybutanoic acid. 14,15 To date, MAC reactions have invariably shown a syn diastereoselectivity (syn:anti around 4:1); although the origin of this selectivity has not been probed, it may occur through a Cram-chelate model involving a hydrogen bond between the protected amine and the aldehyde during the first step of the reaction (Scheme 1a). For the further development of this methodology it would be advantageous if the diastereoselectivity could be reversed.…”

“…Both 16 and 17 were observed previously as side products in the studies of the syn-selective MAC reaction conducted on N-Boc-O-benzylserinal. 14 In those studies, the syn diastereomer of 17 was transformed into a syn α-hydroxyβ-aziridino ester. 14 To complement that work, 17 was tosylated in excellent yield to give 18, which was cyclized upon treatment with sodium hydride, giving the corresponding anti α-hydroxy-β-aziridino ester 19 (Scheme 2).…”

“…14 In those studies, the syn diastereomer of 17 was transformed into a syn α-hydroxyβ-aziridino ester. 14 To complement that work, 17 was tosylated in excellent yield to give 18, which was cyclized upon treatment with sodium hydride, giving the corresponding anti α-hydroxy-β-aziridino ester 19 (Scheme 2). This latter derivative is an example of a 2-(carboxymethyl)aziridine, a class of compounds which represent strained β-amino acids.…”