Kishi’s total synthesis

The phenolic oxygen on 2-allyl-4-bromophenol (7) readily underwent oxypalladation using a catalytic amount of PdCl2 and three equivalents of Cu(OAc)2, to give the corresponding benzofuran 8. This process, akin to the Wacker oxidation, was catalytic in terms of palladium, and Cu(OAc)2 served as oxidant [17]. Benzofuran 10, a key intermediate in Kishi s total synthesis of aklavinone [18], was synthesized via the oxidative cyclization of phenol 9 using stoichiometric amounts of a Pd(II) salt. 

N-arylation has been used as the first step in several syntheses of complex molecules. The Ullmann-type reaction of 2-iodo-3-methoxybenzoic acid with l-methylpiperazine-2,5-dione forms the basis of Kishi s total synthesis of dehydrogliotoxin (81T2045) (Scheme 12). 

Hydroxy-lactam 26 (n=2) gave spiroisomer 27 (n=2), albeit in lower yield, under similar conditions. The same authors 191 have also reported the successful cyclization of hydroxy-lactam 29 into spirolactam 30. Analogous results were obtained by Evans and Thomas (10) who found that the cyclization of a 9 1 mixture of enamides 31 and 32 in anhydrous formic acid gave the spirocompound 30. This compound is a key intermediate in Kishi s total synthesis of perhydrohistrionicotoxin (11, 12). 

Control of acyclic stereochemistry. The five contiguous stereocenters of aldehyde 5, an intermediate in Kishi s total synthesis of monensin (6), were established by the hydroboration reactions of 1 and 3, which afforded 2 and 4, respectively, with high stereoselectivity (8 1 diastereomer ratio for 1 12 1 for 3). Kishi argues that the... 

The ABCD segment 538 was then constructed (Scheme 76). The Julia coupling of 528 and 535 followed by methylenation afforded adduct 536. The AB spiroketal system was constructed by functional group manipulation to give 537, which was converted into ketoaldehyde 538 via protective group manipulation and oxidation. The spiroketal 539, which is a key intermediate for Kishi s total synthesis of altohyrtin A (4a), was also synthesized from 537. 

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

Numerous applications of the Ni(n)/Cr(ii)-mediated coupling reaction in total synthesis have already been reported.11 Some of the more noteworthy examples derive from Kishi s laboratories and played a role in the syntheses of such complex molecules as (+)-ophiobolin C16 and halichondrin B17 (see Scheme 5). Another elegant application can be found in the enantioselective total syntheses of (+)-brefeldin C and 4-ep/-brefeldin C by Schreiber and Meyers (see Scheme 5).18... 

The extremely high sensitivity of bacteriochlorins to various reactions makes their chemistry very difficult. This might also be one reason why methods for the total synthesis of bacteriochlorins had not, until very recently, been developed.13 Total synthesis of a tolyporphin model was reported by Kishi et al.13 using an approach that is very closely related to Eschenmoser s syntheses of hexahydroporphyrins from reduced linear tetrapyrroles by cyclization (see Section 1.5.1). 

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-... 

Katrina L. Jackson obtained her B.S. degree in biochemistry from Boston College in 2002, where she performed undergraduate research with Professor Shana O. Kelley. In 2007, she obtained her Ph.D. from the University of Colorado-Boulder under the direction of Professor Andrew J. Phillips. Currently, she is a postdoctoral researcher at Harvard University with Professor Yoshito Kishi. Her research interests are focused on the total synthesis of biologically active natural products. 

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... 

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