Studies towards the total synthesis of cruentaren A and B: Stereoselective synthesis of fragments C1-C11, C12-C22 and C23-C28

• Published in: Tetrahedron letters 2017-07, Vol.58 (28), p.2685-2689
• Main Authors: Ganganna, Bogonda, Srihari, Pabbaraja, Yadav, Jhillu Singh
• Format: Article
• Language: English
• Subjects: Alder-Rickert reaction; Pirrung-Heathcock’s aldol; Resorcylic acid lactones; Sharpless epoxidation
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2017.05.034

[Display omitted] •Three key fragments C1-C11, C12-C22 and C23-C28 of cruentaren were synthesized.•Achieved Pirrung-Heathcock’s anti aldol reaction with good diastereoselectivity.•Regioselective Alder-Rickert reaction was successfully utilized for aromatic fragment.•C1-C11 fragment was accomplished very effectively with 25.8% overall yield.•C12-C22 fragment was accomplished efficiently in 15 steps with 11.6% overall yield. A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn-stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti-stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis-2-butene-1,4-diol respectively.