Yamaguchi lactonization

AT-Boc group, was followed by reductive debenzylation of 30 and Yamaguchi lactonization of the resultant hydroxy acid to provide macrodiolide 31 in 25% yield accompanied by a dimer. Finally, removal of the N-Boc group and reductive N-methylation yielded pamamycin-607 (lb). In total, ca. 40 steps were required to access the target from ester 4, aldehyde 22, and allyl stannanes 10 and ent-lO. 

In fact, the sensitive disubstituted alkene of 14 turned out to not be stable to the subsequent A1C1, coupling conditions, so the alkene and the secondary alcohol were protected together as the bromoether 15. Condensation of the derived enol ether 16 with the sulfone 2 in the presence of DTBMP (2,6-di-/-butyl-4-methylpyridine) then gave 17. Yamaguchi lactonization followed by regeneration of the alkene by zinc reduction completed the synthesis of 1. 

YAMADA Coupling reagent 430 YAMAGUCHI Lactonization reagent 431 YAMAZAKI Cyanoandme synthesis 432 Yamamoto 177... 

An enantioselective total synthesis of epothilone A 837 using multifunctional asymmetric catalysis has been achieved [614]. Suzuki cross-coupling of fragment A 835 with fragment C 836 followed by Yamaguchi lactonization as key steps leads to an enantiocontrolled synthesis of epothilone A 837. During the synthesis of fragment A, reaction of an aldehyde 832 with TMS-acetylide affords an alcohol, which... 

Rao synthesized the unnatural (-b)-cephalosporolide D (ent-1) using the Yamaguchi lactonization method [58]. Cyclization of the seco-acid 41 activated by 2,4,6-trichlorobenzoyl chloride and a catalytic amount of DMAP formed eight-membered lactone 42 in 68% yield (Scheme 5.13). 

Wills first accomphshed the total synthesis of 6a using the Yamaguchi lactonization to form the medium-sized lactone of 6a (Scheme 5.31) [80]. Lactonization of 87 was achieved by employing Yamaguchi s mixed-anhydride method to form the corresponding lactone 88 [26]. Although the preparation of the nine-membered lactone moiety can be difficulL smooth lactonization was accomphshed because the cis double bond provides both enthalpic and entropic assistances to this process, in contrast with cychzation of a saturated ring. 

This method offers a useful alternative to more typically employed Yamaguchi lactonization and RCM-mediated macrocydization methods. 

Pan and collaborators [87] reported a more conventional approach to aigialomycin D exploiting a Yamaguchi lactonization for macrocyclization. Key features of the route included a SAE and selective opening of epoxy alcohol 222 to install the C5, C6 -diol and two Julia-Kocienski couplings to establish the -configured double... 

Horita, K, Nagasawa, M., Hachiya, S., Sakurai, Y, Yamazaki, T, UenishL J., and Yonemitsu, O. (1997) Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. 8. Synthesis of the lactone part (C1-C36) via Homer-Emmons coupling between C1-C15 and C16-C36 fragments and Yamaguchi lactonization. Tetrahedron Lett., 38, 8965-8968. 

Other groups have also used the Yamaguchi lactonization procedure to synthesize natural products, most notably Seebach in the synthesis of (+)-myscovirescine M2, a 27-membered lactone, in which the seco acid was converted to the lactone in 83% yield. Symmetrical diolides (8) have been prepared from unprotected seco acids in fair yields (eq 4) when other lactonization procedures failed. Unsymmetrical diolides require protected seco acids. ... 

Mote recently, treatment of 3-hydroxybutanoic acid (9) under the Yamaguchi lactonization conditions of high dilution gave, in... 

The Yamaguchi lactonization also leaves intact any stereochemistry at the carbon bearing the hydroxyl group. This is in contrast to the Mitsunobu lactonization, which inverts that stereochemistry (eq7). ... 

The tendency of the Yamaguchi lactonization conditions to form diolides from some seco acids, as shown by Seebach, can also pose a problem. Steglich has shown that some a,u)-hydroxy acids (13) tend to dimerize under the Yamaguchi lactonization conditions. However, by using a modified Mitsunobu lactonization, the monolide was obtained in 59% yield (eq 9). All other lactonization procedures also gave varying amounts of diolide, including the standard Mitsunobu lactonization procedure. ... 

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