Novel azalides derived from 16-membered macrolides. Part II: Isolation of the linear 9-formylcarboxylic acid and its sequential macrocyclization with an amino alcohol or an azidoamine.

Abstract:

:The design and synthesis of novel 14- to 16-membered 11-azalides starting from 16-membered macrolides are reported. A linear 9-formylcarboxylic acid was isolated via a mobile dialdehyde previously reported. Sequential macrocyclization of the formylcarboxylic acid with amino alcohol followed by deprotection afforded corresponding 14- to 16-membered azalides. On the other hand, reductive amination of the formylcarboxylic acid with an azidoamine followed by macrolactam formation with an amine generated from the azide gave 14- to 16-membered azalactams. Among these derivatives, 15-membered azalactams and 16-membered azalides exhibited characteristic in vitro antibacterial activities. Although optimization of 15-membered azalactams including demycarosyl analogues did not provide remarkably promising molecules, SAR studies of 16-membered azalides disclosed that substitution at the 15 position was very important for identification of a clinical candidate.

journal_name

Bioorg Med Chem

authors

Miura T,Kanemoto K,Natsume S,Atsumi K,Fushimi H,Yoshida T,Ajito K

doi

10.1016/j.bmc.2008.09.054

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

10129-56

issue

23

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(08)00905-X

journal_volume

16

pub_type

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