Novel approach to the zaragozic acids. Enantioselective total synthesis of 6,7-dideoxysqualestatin H5.
The total synthesis of 6,7-dideoxysqualestatin H5 (3) has been completed by a concise approach that features the stereoselective intramolecular vinylogous aldol reaction of the furoic ester 25a to give 30 or its trimethylsilyl ether derivative 34, which possess the requisite absolute stereochemistry at C(3)-C(5) of 3. Compound 34 was reduced to the saturated bislactone 39, and the C(1) side chain subunit 47 was introduced leading to a mixture of the hemiacetals 48 and the corresponding ketone 49. When this mixture was stirred with methanolic acid, transketalization occurred to give a mixture of 50 and the spirocyclic methyl acetals 51a,b. Oxidation of the primary alcohol group in 50 followed by saponification of the two remaining ester groups gave 3. The longest linear sequence in the synthesis commences with commercially available erythronolactone (26) and requires 17 chemical steps with only 10 isolated intermediates.
Naito
Satoru
S
Department of Chemistry and Biochemistry, The University of Texas, Austin 78712, USA.
Escobar
Maya
M
Kym
Philip R
PR
Liras
Spiros
S
Martin
Stephen F
SF
D000080:Acetals / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D007659:Ketones / Q000737:chemistry; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014233:Tricarboxylic Acids / Q000138:chemical synthesis*
C465981:6,7-dideoxysqualestatin H5; D000080:Acetals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007659:Ketones; D007783:Lactones; D014233:Tricarboxylic Acids; C075117:squalestatin 1