Enantioselective Total Synthesis of (+)-6-epi-Mevinolin and Its Analogs. Efficient Construction of the Hexahydronaphthalene Moiety by High Pressure-Promoted Intramolecular Diels−Alder Reaction of (R,2Z,8E,10E)-1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-2,8,10-dodecatrien-4-one

Abstract

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, (+)-6-epi-mevinolin (2a) and (+)-6-epi-4a,5-dihydromevinolin (2b), were prepared by combining two nonracemic units, phosphonate 3 and decalin 4, which were prepared from enantiopure 3-substituted pentanedioic acid monoesters 5a and 5b, respectively. Each acid was synthesized from cyclic anhydrides 7a and 7b by diastereoselective ring opening by means of (S)-benzyl mandelate as a common chiral auxiliary. The construction of decalin moiety 4 was accomplished by asymmetric intramolecular Diels-Alder (IMDA) reaction of nonracemic trienone 6 bearing a methyl group as a chiral controller. The IMDA diastereoselectivity of trienone 6 is discussed in terms of the configuration of (E)-and (Z)-dienophiles which are activated by an endogenous carbonyl group. The IMDA reaction of (R)-(Z)-6 under high pressure is highly selective and gives cis-decalins exclusively with preferential formation of 4 over 16. The inhibitory activity of (+)-6-epi-mevinolin (2a) and several analogs against HMG-CoA reductase was compared with mevinolin (1b). (+)-6-epi-Mevinolin (2a) was shown to be half as potent as mevinolin (1b) while (+)-6-epi-4a,5-dihydromevinolin (2b) was as potent as mevinolin.

Property Tuning in Charge‐Transfer Chromophores by Systematic Modulation of the Spacer between Donor and Acceptor

“…66–67 °C]. t BuMe 2 Si‐protected propargyl alcohol was prepared from propargyl acohol and t BuMe 2 SiCl in 93 % yield following literature procedure 25. Final purification was carried out by vacuum distillation (b. p. 27–29 °C at 0.7 Torr) [lit 25.…”

Total Synthesis of Neurymenolide A Based on a Gold‐Catalyzed Synthesis of 4‐Hydroxy‐2‐pyrones

“…A palladium-catalyzed hydrostannylation then provided 14, which was cross-coupled with the known alkenyl iodide 15. [23] This Stille-type reaction was best promoted by copper thiophene-2-carboxylate (CuTC) in the absence of palladium; [24] under these conditions, compound 16 was secured in excellent yield after acetylation of the primary product. This ester was then subjected to a remarkably high yielding, deconjugative Ireland-Claisen rearrangement [25,26] to set three of the four skipped unsaturated sites with the correct Z,E,Z-pattern, as contained within the neurymenolide tether.…”

Total Synthesis of the Antitumor Acetogenin Mosin B: Desymmetrization Approach to the Stereodivergent Synthesis of threo/trans/erythro‐Type Acetogenins

“…Mesylation of 14 followed by iodination gave an iodide 15 (88 % in two steps). The iodide 15 was coupled with the acetylide generated from the tert ‐butyldimethylsilyl (TBS) ether of propargyl alcohol13 on treatment with n BuLi to give alkyne 16 in 74 % yield. Alkylation of 15 with the acetylide generated from an unprotected propargyl alcohol afforded no desired product, and instead, elimination of the iodide occurred due to the basicity of the alkoxide.…”