Radicicol and Monocillin

THREE-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

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

Biosynthetic studies on radicicol involved the identification and characterization of the gene cluster, performed independently by two different groups who worked with two different radicicol-producing fungi Pochonia chlamydosporia and C. chiver-sii [428,438]. 

Rdc5 KS MAT DH core ER KR ACP Rdcl gAt)CKS (S AT CTr (Sa CT Tetraketide Tetraketide Pentaketide Hexaketide 

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

Turbyville TJ, Wijeratne EMK, Liu MX, Bums AM, Seliga CJ, Luevano LA, David CL, Faeth SH, Whitesell L, Gunati-laka AAL. Search for hsp90 inhibitors with potential anticancer activity isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the sonoran desert. J. Nat. Prod. 2006 69 178-184. 

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

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

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... 

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... 

Lampilas M, Lett R (1992) Convergent Stereospecific Total Synthesis of Monocillin I and Monorden (or Radicicol). Tetrahedron Lett 33 777... 

Tinchkowski I, Lett R (2002) Improvements of the Total S50ithesis of Monocillin I and Radicicol via Miyaura-Suzuki Couplings. Tetrahedron Lett 43 4003... 

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