Monocillin

Fig. 1. Partial structure-activity relationships for radicicol (11) and monocillin (12).

Danishefsky s total synthesis of 317 and its chlorine free precursor monocillin I 316 features an RCM reaction with a substrate 310 that in addition to a dithiane protective group contains a vinyl epoxide and a diene moiety at... 

Wicklow DT, Joshi BK, Gamble WR, Gloer JB, Dowd PF (1998) Antifungal Metabolites (Monorden, Monocillin IV, and Cerebrosides) from Humicola fuscoatra Traaen NRRL 22980, Mycoparasite of Aspergillus flavus Sclerotia. Appl Environ Microbiol 64 4482... 

The tolerance of the RCM reaction to diverse functional groups is illustrated by the synthesis of 14-membered macrocycles monocillin I and radicicol, reported by Danishefsky and coworkers [63]. In the presence of catalyst G2, cyclization of dienic substrates 90 and 91, which comprise an allylic epoxide and a ketone function protected as a dithiane, occurs in 55-60% yields, generating intermediate macrocy-clic dienes 92 and 93 of 6E,ttZ stereochemistry (Scheme 2.36). It is interesting to... 

Another example involves the parasitism of one fungus on another. The parasitism of Monocillium nordinii on the pine stem rust fungi Cronartium coleosporioides and Endocronartium harkenssii is due to production of the antifungal antibiotics monorden and the monocillins [61]. 

Lampilas M, Lett R (1992) Convergent Stereospecific Total Synthesis of Monochiral Monocillin I Related Macrolides. Tetrahedron Lett 33 773... 

Tinchkowski I, Lett R (2002) Convergent Stereospecific Total Synthesis of Monocillin I and Radicicol Some Simplifications and Improvements. Tetrahedron Lett 43 3997... 

Garbaccio RM, Stachel SJ, Baeschlin DK, Danishefsky SJ (2001) Concise Asymmetric Syntheses of Radicicol and Monocillin I. J Am Chem Soc 123 10903... 

Figure 3.122 Structure of radicicol 365, synonymous with monorden, and monocillin 1366.

Monocillin 1366, as well as other monocillins, is a shunt metabolite of the radicicol biosynthesis [438]. 

Figure 3.123 Proposed biosynthetic pathway to monocillin II366, early intermediate in the biosynthesis of radicicol.

Figure 3.124 Proposed biosynthetic pathway from monocillin II to radicicol and the pathway...

Such applicability of the RCM reactions to form conjugated diene or polyene systems in macrocyclic rings has come under close scrutiny in recent years. The Danishefsky group employed the RCM macrocycliza-tions of diene-ene systems in total syntheses of resorci-nylic macrolides, radicicol 40 and monocillin (41, Scheme 24.12). The both macrolides are isolated from Monocillium nordinii and exhibit a variety of antifungal and antibiotic properties. The common intermediate 38 was synthesized from commercially available 36. Grubbs catalyst [Ru]-II exerted its effect on the RCM between the alkenyl oxirane and the diene functions of... 

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