Manumycin family

The manumycin family were isolated from Streptomyces parvulus (Tii 64) and possess a wide range of biological properties. Taylor and co-workers synthesized manumycin A (7) via the quinone monoacetal (131), which was prepared by PIDA oxidation, followed by epoxidation and alkylation on the cyclohexa-dienone (130) [90] (Scheme 8). Other members of the mamumycin family of antibiotics such as alisamycin, asukamycin, and ( )-nisamycin (8) have been synthesized by similar strategies [91]. 

The extremely broad functional group tolerance of the Pd-catalysed N-de protection of Aloe groups was a crucial design feature in a synthesis of the epoxy-quinol core of the Manumycin family of antitumour antibiotics [Scheme 8,80].195 Note the convenient generation of the Pd(0) catalyst in situ from reaction of dichlorobis(triphenylphosphine)palladium(II) with tributylstannane. The use of sodium borohydride and borane dime thy lamine complex is illustrated in Schemes 8.81193 and 8.82194 respectively. 

Manumycin Family and Other Amides Derived from 2-Amino-3-hydroxy-cyclopenten-2-one... 

The manumycin family is a group of antibiotics produced by the Streptomyces species. They are structurally-related natural products and are exemplified by alisamycin (48), asukamycin (49), U-56407 (50), colabomycin A (51), manumycins A (52), B (53), C (54) and D (55), and nisamycin (56). Similar structural moieties are present in all members of the group a mC7N unit with an epoxyenone structure containing two... 

Figure 3.71 Proposed pathway for assembly of mC N units in the manumycin family antibiotics.

Enantioselective oxidation is one of the most important and yet useful transformations in organic synthesis, and the asymmetric phase-transfer catalysis has made notable contributions to this field. The stereoselective epoxidation of electron-deficient olefins with peroxides is a representative example, and Taylor demonstrated the synthetic utility of this system by accomplishing the total syntheses of three natural products of manumycin family, (-l-)-MT 35214 131, (-l-)-manumycin A 132, " and (—)-alisamycin 133 (Scheme 4.31). The syntheses were undertaken by the... 

SCHEME 4.31. Synthetic utilities of PTC-oxidation for the synthesis of manumycin family. 

Macdonald G, Alcaraz L, Lewis NJ, Taylor RJK. Asymmetric synthesis of the mC7N core of the manumycin family Preparation of (+)-MT 35214 and a formal total synthesis of (—)-alisamycin. Tetrahedron Lett. 1998 39(30) 5433-5436. 

Figure 3.68 Structures of the manumycin, asukamycin, and related family of antibiotics.

Biosynthetic studies on this family of antibiotics were conducted in parallel on the major components of the group, namely manumycin 220 and asukamycin 221, because of their remarkable similarities, although they differ from each other in the nature of their side chains. 

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