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Discovery, Characterization, and Analogue Synthesis of Bohemamine Dimers Generated by Non‐enzymatic Biosynthesis
Author(s) -
Fu Peng,
Legako Aaron,
La Scott,
MacMillan John B.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201600024
Subject(s) - cytotoxicity , derivatization , chemistry , enzyme , biosynthesis , a549 cell , monomer , formaldehyde , stereochemistry , alkyl , aryl , streptomyces , chemical synthesis , cell culture , methylene , combinatorial chemistry , organic chemistry , biochemistry , in vitro , biology , bacteria , high performance liquid chromatography , polymer , genetics
Dibohemamines A–C ( 5 – 7 ), three new dimeric bohemamine analogues dimerized through a methylene group, were isolated from a marine‐derived Streptomyces spinoverrucosus . The structures determined by spectroscopic analysis were confirmed through the semi‐synthetic derivatization of monomeric bohemamines and formaldehyde. These reactions, which could occur under mild conditions, together with the detection of formaldehyde in the culture, revealed that this dimerization is a non‐enzymatic process. In addition to the unique dimerization of the dibohemamines, dibohemamines B and C were found to have n m cytotoxicity against the non‐small cell‐lung cancer cell line A549. In view of the potent cytotoxicity of compounds 6 and 7 , a small library of bohemamine analogues was generated for biological evaluation by utilizing a series of aryl and alkyl aldehydes.