Cochrane Stephen A, Surgenor Richard R, Khey Kevin M W, Vederas John C
Department of Chemistry, University of Alberta , Edmonton, Alberta T6G 2G2, Canada.
Org Lett. 2015 Nov 6;17(21):5428-31. doi: 10.1021/acs.orglett.5b02779. Epub 2015 Oct 14.
The isolation and total synthesis of the antimicrobial lipopeptide cerexin A1 is reported. This synthesis includes the preparation of orthogonally protected γ-hydroxylysine, utilizing a nitrile Reformatsky-type reaction as a key step to yield both diastereomers more efficiently than previously reported methods. The configuration of the β-hydroxyl in the lipid tail was determined by the use of a modified Ohrui-Akasaka approach. Furthermore, new cerexin analogues from Bacillus mycoides ATCC 21929 were isolated and characterized, revealing an ε-amino succinylation of a hydroxylysine residue that is unusual in a nonribosomal peptide synthetase product.
报道了抗微生物脂肽cerexin A1的分离和全合成。该合成包括制备正交保护的γ-羟基赖氨酸，利用腈类Reformatsky型反应作为关键步骤，比先前报道的方法更有效地生成两种非对映异构体。通过使用改良的大仓赤坂方法确定了脂质尾部β-羟基的构型。此外，从蕈状芽孢杆菌ATCC 21929中分离并表征了新的cerexin类似物，揭示了羟基赖氨酸残基的ε-氨基琥珀酰化，这在非核糖体肽合成酶产物中并不常见。
