Sponges, cytotoxic macrolides

Carbonelli, S. S. Zampella, A. Randazzo, A. Debitus, C. Gomez-Paloma, L. (1999) Sphinxolides E-G and reidiaspongiolide C four new cytotoxic macrolides from the New Caledonian Lithistida sponges N. superstes and R coerulea. Tetrahedron, 55, 14665-74. 

Marine sponges of the genus Haliclona contain a diverse array of active secondary metabolites, including highly potent cytotoxic macrolides, e g., halichondrin and related compounds, Fig. (56) [468], and salicylihalamides A and B, Fig. (57) [469], New macrolides chemically related to salicylihalamides, apicularens A and B, were recently isolated from the myxobacteria Chondromyces sp. [470], From marine bacteria, other cytotoxic macrolides have been isolated, such as octalactin A, Fig. (58) and B, which have been shown as a cell cycle-specific anticancer drug [471], and swinholide, Fig. (59), isolated from symbiotic cyanobacteria with the marine sponge Theonella swinhoei [472]. 

Sandler JS, Colin PL, Kelly M, Fenical W (2006) Cytotoxic Macrolides from a New Species of the Deep-Water Marine Sponge Leiodermatium. J Org Chem 71 7245... 

The compounds isolated from the nudibranch Hexabranchus sanguineus varied with collecting location but usually included dihydrohalichondra-mide (261) and tetrahydrohalichondramide (268). Compounds 261, 263, 265, and 268 show antifungal activity and inhibit cell division in the fertilized sea urchin egg assay (218). Three cytotoxic macrolides, mycalolides A-C (269-271), were isolated from a Japanese sponge of the genus My-cale, and their structures were elucidated to be hybrids of ulapualides and halichondramide (219). 

Fusetani, N., Shinoda, K., and Matsunaga, S., Cinachyrolide A a potent cytotoxic macrolide possessing two spiro ketals from marine sponge Cinachyra sp., J. Am. Chem. Soc., 115, 3977, 1993. 

Kobayashi, M., Aoki, S., Sakai, H., Kihara, N., Sasaki, T., and Kitagawa, I., Altohyrtins B and C and 5-desacetylaltohyrtin A, potent cytotoxic macrolide congeners of altohyrtin A, from the Okinawan marine sponge Hyrtios altum, Chem. Pharm. Bull., 41, 989, 1993. 

Kitagawa, I., Kobayashi, M., Katori, T., Yamashita, M., Tanaka, J., Doi, M., and Ishida, T., Absolute stereostructure of swinholide A, a potent cytotoxic macrolide from the Okinawan marine sponge Theonella swihnoei, J. Am. Chem. Soc., 112, 3710, 1990. 

In the first example, 2D NOESY spectra were used to define the stereochemistry in the synthetic cycloadduct 8.14 [7], a potential biomimetic precursor to the naturally occurring marine-sponge alkaloid Keramaphidine B, 8.15. This problem is essentially the same as that addressed for 8.7 above using the NOE difference experiment, but in this case the additional unsaturated sidechains caused extensive overlap in the proton spectrum and precluded the use of selective presaturation. Sufficient characteristic NOEs present in a 600 ms NOESY spectrum gave conclusive proof of the endo stereochemistry, as shown. Only positive NOEs were observed, consistent with a molecule of mass 436 daltons in chloroform. NOESY spectra have also been successfully applied to the structure elucidation of molecules for considerably greater mass and complexity, as illustrated by the cytotoxic macrolide cinachyrolide A, 8.16 [35], also from a marine sponge. The structure of the molecule was determined through extensive 600 MHz 2D NMR experiments, of which NOESY played... 

D Auria, M. V., Debitus, C., Paloma, L. G., Minale, L., and Zampella, A. (1994). Superstolide A A potent cytotoxic macrolide of a new type from the New Caledonian deep water marine sponge Neosiphonia superstes. J. Am. Chem. Soc. 116, 6658-6663. 

Swinholide A (34), a potent cytotoxic macrolide, was first isolated from the Red Sea sponge Theonella swinhoei in 1985 and its structure was first proposed as a monomeric 22-membered macrocyclic lactone [71]. In 1990, swinholide A... 

Tanaka, J., and Higa, T. (1996). Zampanolide, a new potent cytotoxic macrolide from a marine sponge. Tetrahedron Lett. 37, 5535-5538,... 

West, L. M., Northcote, P. T, and Battershill, C. N. (2000). Peloruside A A potent cytotoxic macrolide isolated from the New Zealand marine sponge Mycale sp. J. Org. Chem. 65,445-449. 

Enantiopure cyclopropanes occur in both nature and medicinal chemistry. Callipeltoside A 4 [2], for example is a moderately cytotoxic macrolide, isolated from the marine sponge Callipelta sp. and contains a trans-chlorocyclopropane side chain. An interesting compound from Eli-Lilly aimed at schizophrenia, which unfortunately fell at Phase II trials is the cyclopropane glutamate analogue LY2140023 which contains four contiguous stereocentres (Fig. 1.3). 

Tanaka, J., Higa, T, Bernardinelli, G., and Jefford, C.W. (1996) New cytotoxic macrolides from the sponge Fasciospongia rimosa. Chem. Lett., 255-256. 

---