Rubrolides

The 4-aryl-2(5// )-furanone unit proved to be present in many naturally occurring (91JOC6275) and medicinally important compounds (93JHC1581). Examples are the potent antibiotics rubrolide A-F 90a-f, isolated by Miao and Andersen from the colonial tunicate Ritterela rubra (Scheme 26) (91JOC6275). 

Reeently, this methodology was used for the straightforward synthesis of the rubrolides 90c and 90e The furanone 92b (Ar = C6H4—OMe) was treated with the appropriate aldehyde 93 or 95 in the presenee of diisopropylamine, followed in situ... 

The diacetates of rubrolide C, D, and E were prepared in 50 to 54% yield, in similar manner. 

Rubrolides A, B, and C (163-165) from the Northeastern Pacific tunicate Ritterella rubra are active against Staphylococcus aureus (MIC 9, 2 and 11 pg/disk) and Bacillus subtilis (MIC 9, 2 and 11 pg/disk). The most active compound, rubrolide B, contains an additional chlorine atom [126]. 

Ortega MJ, Zubia E, Ocana JM, Naranjo S, Salva J (2000) New Rubrolides from the Ascidian Synoicum blochmanni. Tetrahedron 56 3963... 

Pearce AN, Chia EW, Berridge, MV, Maas EW, Page MJ, Webb VL, Harper JL, Copp BR (2007) E/Z-Rubrolide O, an Anti-inflammatory Halogenated Furanone from the New Zealand Ascidian Synoicum n. sp. J Nat Prod 70 111... 

Boukouvalas J, Lachance N, Ouellet M, Tmdeau M (1998) Facile Access to 4-Aryl-2(5//)-furanones by Suzuki Cross Coupling Efficient Synthesis of Rubrolides C and E. Tetrahedron Lett 39 7665... 

Nice applications of this sequential method are the concise syntheses of rubrolide diacetates A, C, D, and E (142) (Z/E ratios of > 50 1) (Scheme 54) that were converted into the rubrolides (R = H) by saponification of the acetates with methanolic K2CO3 in MeOH/THF (1 1). 

Similar metabolites which appear to be derived from tyrosine and brominated tyrosine include botryllamides A-D (31-34), which were isolated from brightly coloured styelid ascidians from the genus Botryllus collected in Fiji and in Australia [32]. Botryllamide D was reported to exhibit marginal cytotoxicity after 72 hour exposure to the human colon cancer cell line HCT 116 (IC50 17 pg/mL), but were inactive in vivo. The rubrolides, which were isolated from Riterella rubra [33] may well be derived from precursors similar to the botryllamides, however, the rubrolides are not alkaloids so have been mentioned here only for comparative purposes. 

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