Total synthesis of rifamycin

Among the syntheses of complicated natural products, the total synthesis of rifamycin S (44) is another example that shows how a complicated structure can be constructed by applying the concept of double asymmetric synthesis (see Section 1.5.3 for double asymmetric synthesis). Rifamycin S is one of the an-samycin antibiotics, characterized by a distinct structural feature a macro-... 

The total synthesis of rifamycin S was one of Kishi s many achievements in organic synthesis.6 Kishi recognized that a certain type of (Z)-olefin such as 51 tends to take a conformation in which C-l, C-2, C-3, and H-3 are nearly co-... 

Studies on the total synthesis of rifamycin S (102) were initiated by Corey et al., [184] and then carried out in a complete form by Kishi et al... 

Mootoo and Fraser-Reid have given full accounts of their synthesis of a chiral unit corresponding to the ansa-chain of streptovaricin A (see Vol. 23, p. 270),34,35 and Tatsuta and Kinoshita s group has reported in full on the total synthesis of rifamycin W, using an ansa-chain unit constructed from D-glucose-derived starting materials (Bull. Chem. Soc. Jpn., 1985, 5, 3457), but with some improved procedures.3 6... 

A notable achievement in this area is the total synthesis of ( )-rifamycin S by Kishi s group.The vital ring-closure step has also been effected by Corey and Clark. 

USE As intermediate in total synthesis of rifamycine S segment (compound 16b) [7876]. 

SCHEME 22.45. Kishi et al. s retro-synthesis of rifamycin S. Expeditious asymmetric synthesis of a stereoheptad formal total synthesis of rifamycin S. 

Kishi Y. Total synthesis of rifamycin-S. Pure Appl. Chem. 1981 53(6) 1163-1180. 

The high syn stereoselectivity attained in zirconium enolate aldol reactions has proved useful in complex natural product synthesis. The zirconium-mediated aldol reaction of the chiral ethyl ketone (9) with a chiral aldehyde has been used by Masamune et al. to give selectively adduct (10), which was further elaborated into the ansa chain of rifamycin S (equation 1). Good enolate diastereofacial selectivity is also obtained here and leads to a predominance of one of the two possible syn adducts. A zirconium enolate aldol reaction also features in the Deslongchamps formal total synthesis of erythromycin A, where the di(cyclopentadienyl)chiorozirconium enolate from methyl propionate adds with high levels of Cram selectivity to the chiral aldehyde (11) to give the syn adduct (12 equation 2). A further example is... 

Danishefsky and coworkers employed two hetero Diels-Alder reactions in a total synthesis of the ansa bridge of rifamycin S (Scheme 52) The first cyclocondensation reaction uses the trimethylsilyloxy diene (14) and a preincubated solution of 3-(benzoyloxy)-2-methyl-1-propanal (188) with an excess of TiCU in CHCh. The product is exclusively the syn-ACF pyrone (189). Through a Ferrier rearrangement and a sequence of oxidation-reduction steps followed by functional group manipulations aldehyde (190) is obtained. 

Synthesis of the aliphatic building block of rifamycin S (2) was achieved in 1980 [53], and the total synthesis of racemic 2 was achieved subsequently [53-56]. 

The Ansamycins - 2,12,1 Rifamvcins. The c.d, spectrum of rifamycin 5 (171) has been measured and used to derive conformational information Synthetic studies towards rifamycin S have increased during the period under review, and include a total synthesis of (171) by Kishi and co-workers, as outlined below. Using the methods they had earlier developed for the stereocontrolled conversions of X -chiral aldehydes illustrated in Scheme 34, these workers have assembled the —CH(Me)CH(DR)— backbone (C-20 to C-27) of... 

Tarara G, Hoppe D. Total synthesis of protected D-altro-3,6-dideoxy-3-C-methylhexose and D-galacto-3,6-dideoxy-3-C-methyUiexose-key intermediates of a rifamycin S synthesis. Synthesis 1989 (2) 89-92. 

Rifamycin W (104) was isolated from a mutant strain of Norcardia mediterranei [187] and its structure was determined [188] on the basis of spectroscopic studies in comparison with rifamycin S (102). Rifamycin W (104) is transformed by the parent Norcadia strain into rifamycin S and therefore is thought to be the biosynthetic intermediate of all the rifamycins [187]. The total synthesis carried out by Tatsuta et al. has allowed the elucidation of the complete stereochemistry of compound (104) [189]. The synthesis has been accomplished by coupling the segments of the aliphatic ansa-chain (E) and the aromatic nucleus (F). 

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