Cytostatic activity, chemical structure

An important group of secondary metabolites from bryozoans consists of the macrocyclic lactones which have been obtained from Bugula neritina. These compounds have potential as leads for future anticancer drugs. Bryostatins 1-15 are bryopyran lactones, 1-15, which have very selective antineoplastic and cytostatic activity. Bryos-tatin 1, 1, is undergoing clinical evaluation. Chemical components of B. neritina vary somewhat depending on the area of its collection. The isolation, structural elucidation and biological activity of bryostatins 1-13 have been reviewed [5]. 

Kendomycin (13) was isolated from different Streptomyces species, which showed potent antibacterial and cytostatic activities [36, 37]. Due to its challenging chemical structure and interesting biological profile, a number of impressive total syntheses have been accomplished [38]. However, all attempts to achieve 13,14-macrocyclization and formation of the desired 13,14- -olefin by alkene RCM were unsuccessful [39-41]. In 2009, Mulzer and coworkers described a novel approach to the total synthesis of kendomycin (13) via the selective alkene RCM at ClO-Cll as one of the key steps (Fig. 5) [42]. In this work, they demonstrated that RCM with Grubbs II catalyst smoothly facilitated ring closure to form the 10,ll- -olefin (15)... 

A known strain of S. antibioticus was found to produce a compound designated simocyclinon D8 (44) [31]. The compound exhibits antibiotic activity against Gram-positive bacteria and cytostatic effects against various cancer cells. Its structure and biosynthesis were clarified on the basis of physical-chemical methods, mainly by ID and 2D NMR and ESI-MS. It was found that during its biosynthesis the incorporation of 180 into the aminocoumarine residue is probably catalyzed by a monooxygenase. 

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