Rhizoxin

Total synthesis of antitumor macrolide rhizoxin 97YZ486. 

A similar cross-coupling reaction was used for macrocylization in the synthesis of rhizoxin A.209... 

Structure 1 vinblastine, 2 vincristine, 3 maytansine, 4 rhizoxin and 5 paclitaxel (Taxol)... 

Catharanthus roseus) [9]. Maytansine (3) is an ansa macrolyde isolated from Maytenus ovatus [10], and rhizoxin (4) is an antitumor macrolide isolated from the fungus Rhizopus chinensis [11]. Another very important tubulin interactive anti-cancer agent is colchicine (6), and this compound binds to a different binding site of tubulin but is also used in anti-cancer therapy. 

The macrocyclic lactone antibiotic rhizoxin, obtained from a plant fungus, has been reported to have activity against vincristine-resistant cells, both in vitro and in vivo (34). Such observations are interesting in view of the similar effects of rhizoxin and vincristine on cell morphology and cell cycle distribution. 

New methods for the synthesis of 2,4-disubstitued oxazoles are summarized in a recent review. 2-Alkyl-1,3-oxazoles bearing alkyl, aryl, or acyl substitution at C4 are common substructures in natural products. Examples include macrolides such as rhizoxin (4), hennoxazole A (5), and phorboxazole A (6), ° as well as many cyclic peptides that incorporate an oxazole subunit presumably derived from serine. ... 

Rhizoxin (NSC 332598) Stella etal. (1988) Solubilization in emulsion formulation for slow infusion... 

Kurihara, A., Shibayama, Y., Mizota, A., Yasuno, A., Ikeada, M., and Hisaoka, M. (1996) Pharmacokinetics of highly lipophilic autitumor agent palmitoyl Rhizoxin incorporated in lipid emulsion in rStsl. 

Masamune s norephedrine-based anti -aldol methodology was again employed successfully in the total synthesis of the antitumor macrolide natural product rhizoxin D (17)7 (Scheme 2.2g). The synthesis began with an anti-aldol addition of boron enolate of 3-ent to the aldehyde 18. The addition proceeded with... 

The segment linkage step in a synthesis of Rhizoxin D [129] consists of the coupling of 6-branched saturated sulfone 291 (Scheme 94) with a,P-unsaturated aldehyde 290. The reaction was carried out with LHMDS in THE... 

In another approach to Rhizoxin D, olefination with the use of a BT sulfone was also used [130]. 

Figure 10 Rhizoxin, a polyketide from bacterial endosymbionts of the pathogenic fungus Rhizopus microsporus.

Sato Z, Matsuda I, Noda T. Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin rhizoxin produced by Rhizopus chinensis. J. Antibiot. 1984 37 354-362. 

Tsuruo T, Oh-hara T, lida H, Tsukagoshi S, Sato Z, Matsuda I, Iwasaki S, Okuda S, Shimizu F, Sasagawa K, Fukami M, Fukuda K, Arakawa M. Rhizoxin, a macrocychc lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines. Cancer Res. 1986 46 381-385. 

Scherlach K, Partida-Martinez LP, Dahse HM, Hertweck C. Antimitotic rhizoxin derivatives from a cultured bacterial endosym-biont of the rice pathogenic fungus Rhizopus microsporus. J. Am Chem. Soc. 2006 128 11529-11536. 

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