Sporolides A and B are polycyclic macrolides extracted from the obligate marine bacteriumSalinispora tropica, which is found in ocean sediment. They are composed of a chlorinated cyclopenta[a]indene ring and a cyclohexenone moiety.[1] They were the second group of compounds (after salinosporamide A) isolated from Salinispora, and were said to indicate the potential of marine actinomycetes as a source of novel secondary metabolites.[2] The structures and absolute stereochemistries of both metabolites were elucidated using a combination of NMR spectroscopy and X-ray crystallography.
The complex aromatic structure of the sporolides was hypothesized to be derived from an unstable nine-membered ring enediyne precursor, which could undergo Bergman cyclization to generate a para-benzyne intermediate. Nucleophilic attack by chloride would account for the 1:1 mixture of sporolide A and B and for the single chlorine in these enediyne-derived natural products. This proposed mechanism was demonstrated in laboratory experiments,[3]
Biosynthesis
The biosynthesis of sporolide A and B is related to that of enediynes such as dynemicin A[4] and is proposed to proceed as shown below.[1][3]
Chemical synthesis
The first total synthesis of sporolide B was reported by K. C. Nicolaou's group and used a highly stereoselective and convergent strategy that involved two cycloaddition reactions. The first was a ruthenium-catalyzed intermolecular [2+2+2] cycloaddition reaction between two acetylenic units, A and B, and the second a thermally induced intramolecular [4+2] cycloaddition reaction between an o-quinone and the tetrasubstituted olefin within the intermediate, forming the macrocyclic structure of the target product.[5][6]
References
^ abMcGlinchey, Ryan P.; Nett, Markus; Moore, Bradley S. (2008). "Unraveling the Biosynthesis of the Sporolide Cyclohexenone Building Block". Journal of the American Chemical Society. 130 (8): 2406–2407. doi:10.1021/ja710488m. PMID18232689.
^Buchanan, Greg O.; Williams, Philip G.; Feling, Robert H.; Kauffman, Christopher A.; Jensen, Paul R.; Fenical, William (2005). "Sporolides a and b: Structurally Unprecedented Halogenated Macrolides from the Marine Actinomycete Salinisporatropica". Organic Letters. 7 (13): 2731–2734. doi:10.1021/ol050901i. PMID15957933.
^ abPerrin, Charles L.; Rodgers, Betsy L.; O'Connor, Joseph M. (2007). "Nucleophilic Addition to a p-Benzyne Derived from an Enediyne: A New Mechanism for Halide Incorporation into Biomolecules". Journal of the American Chemical Society. 129 (15): 4795–4799. doi:10.1021/ja070023e. PMID17378569.