Synthesis of the proposed structure of mucoxin via regio- and stereoselective tetrahydrofuran ring-forming strategies.
An enantioselective total synthesis of the proposed structure of mucoxin (1) is described. Mucoxin, an annonaceous acetogenin isolated from bioactive leaf extracts of Rollinia mucosa, is the first acetogenin containing a hydroxylated trisubstituted tetrahydrofuran (THF) ring. This natural product is a highly potent and specific antitumor agent against MCF-7 (breast carcinoma) cell lines (ED50 = 3.7 x 10(-3) microg/mL compared to adriamycin, ED50 = 1.0 x 10(-2) microg/mL). The total synthesis described herein features two regio- and stereoselective THF ring-forming reactions. The 2,3,5-trisubstituted THF portion (C13-C17) was accessed using a highly regioselective cyclization of a methylene-interrupted epoxydiol, and the 2,5-disubstituted THF ring (C8-C12) was conveniently assembled via a 1,2-n-triol cyclization strategy. The spectral data of the synthetic material and two of its diastereomers did not match the reported data for the natural product. On the basis of detailed spectroscopic analysis of the synthesized molecule, we reason that the spectral discrepancies are due to stereochemical misassignment of the natural product.
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Radha S
RS
Narayan
Babak
B
Borhan
D054378:Acetogenins; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D003500:Cyclization; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D031045:Rollinia / Q000737:chemistry; D013057:Spectrum Analysis; D013237:Stereoisomerism
D054378:Acetogenins; D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D005663:Furans; D007783:Lactones; C515333:mucoxin