阿塞拉辛，一种抑制内皮素与其受体结合的新型化合物。II. 结构的分离与解析。

Aselacins, novel compounds that inhibit binding of endothelin to its receptor. II. Isolation and elucidation of structures.

作者信息

Hochlowski J E, Hill P, Whittern D N, Scherr M H, Rasmussen R R, Dorwin S A, McAlpine J B

机构信息

Pharmaceutical Products Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064.

出版信息

J Antibiot (Tokyo). 1994 May;47(5):528-35. doi: 10.7164/antibiotics.47.528.

DOI:10.7164/antibiotics.47.528

PMID:8040049

Abstract

Three novel compounds, named the aselacins, which inhibit the binding of endothelin to its receptor have been isolated from two related Acremonium species of fungi grown in stationary culture. These compounds are cyclic pentapeptolides with a ring formed by cyclo[Gly-D-Ser-D-Trp-beta-Ala-L-Thr] and an additional exocyclic D-Gln to which is attached a functionalized long chain fatty acid. The aselacins differ in the functionalization of this acid. The structures of the aselacins were determined by amino acid analysis, mass spectrometry and evaluation of 1-D and 2-D homonuclear and heteronuclear 1H, 13C and 15N NMR spectra in protic and aprotic solvents. The stereochemistry of the amino acids present was elucidated by chiral HPLC of hydrolyzed compound.

摘要

从在静置培养中生长的两种相关的顶孢霉属真菌中分离出了三种新型化合物，命名为阿塞拉辛，它们可抑制内皮素与其受体的结合。这些化合物是环状五肽内酯，其环由环[甘氨酸-D-丝氨酸-D-色氨酸-β-丙氨酸-L-苏氨酸]形成，还有一个额外的环外D-谷氨酰胺，其上连接有一个功能化的长链脂肪酸。阿塞拉辛在这种酸的功能化方面有所不同。通过氨基酸分析、质谱以及在质子性和非质子性溶剂中对一维和二维同核以及异核1H、13C和15N NMR光谱的评估，确定了阿塞拉辛的结构。通过水解化合物的手性高效液相色谱法阐明了存在的氨基酸的立体化学。