Discovery of New Bohemamines and Synthesis of Methylene‐Bridged Chimeric Derivatives through Natural Product Chimera Strategy

Abstract

Five new pyrrolizidine alkaloids, bohemamines J-N (1-5), were isolated from Streptomyces sp. CPCC 200497. Their structures were assigned based on detailed spectroscopic analysis and semisynthesis. Bohemamine J (1) possesses a new chimeric skeleton derived from bohemamine A (6) and phenylacetaldehyde. Inspired by the nonenzymatic formation mechanism of the methylene-bridged dimers isolated from this strain, we synthesized a series of chimeric derivatives (8, 9, and 12-23) through natural product chimera strategy. Compounds 13, 15, 19, and 21 showed significant antioxidant activity.

Pyrrolizidine Alkaloids—Pros and Cons for Pharmaceutical and Medical Applications

“…Further studies of the Streptomyces sp. CPCC 200497 strain led to the discovery of five new bohemamines J-N [63].…”

Isolation of Hennaminal and Isolation and Total Synthesis of Hennamide, Pyrrolinone Compounds from the Marine Cyanobacterium Rivularia sp.

“…The planar structures of 1 and 2 were established based on 2D NMR spectra, and their absolute configurations were clarified by a combination of computational chemistry and synthetic chemistry. The results clarified that hennaminal ( 1 ) possesses a very rare functional group, β,β-diamino unsaturated ketone, and hennamide ( 2 ) contains a reactive N -acyl pyrrolinone moiety, which spontaneously induces self-dimerization. An evaluation of biological activities using natural 1 and synthetic 2 revealed that hennaminal ( 1 ) and hennamide ( 2 ) had weak selective antitrypanosomal activity.…”

“…We recently discovered two new cyanobacterial metabolites, hennaminal ( 1 ) and hennamide ( 2 ). Hennaminal ( 1 ) possesses a very rare functional group, β,β-diamino unsaturated ketone, which has only been found in bohemamine-type natural products so far . Hennamide ( 2 ) possesses a reactive N -acyl pyrrolinone moiety, which provides both nucleophilicity and electrophilicity.…”

Structurally Diverse Macrolactams from an Antarctic Streptomyces Species

“…Some polycyclic derivatives of polyenic macrolactams are proposed to be produced through nonenzymatic intramolecular cycloadditions and oxidative cyclizations, such as is the case with heronamides, verticilactam, and macrotermycins . Nonenzymatic reactions have been found to be involved in the formation of many complex natural products, including, for example, chimedermycins, pyonitrins, dibohemamines, and discoipyrroles . Thus, as with enzymatic processes, nonenzymatic reactions also play an important role in the formation of natural products.…”