1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Organic & Supramolecular Chemistry Formal Synthesis of Angiopterlactone B via Enantioselective Reduction of Ketone with Daucus Carota Root Navnath B. Khomane, [a, b] Javed S. Patel, [a, c] Prashishkumar K. Shirsat, [a, b] Prakash R. Mali, [a, b] and Harshadas M. Meshram* [a, b] Formal synthesis of angiopterlactone B has been accomplished via. enantioselective reduction of ketone with Daucus carota, Sharpless dihydroxylation and Andos modified Horner-Wads- worth-Emmons (HWE) reagent to introduce Z-olefination. Here we evolved a new path for the synthesis of (S,S)-osmundalac- tone and 3–5 dihydroxy g-caprolactone. The initial synthetic route for both caprolactone and osmundalcactone build on biocatalytic process while in later case Sharpless dihydroxyla- tion delivered required stereocentres. Z-selective olefination was utilized to furnish caprolactone which was further recycled in to 1-(5-oxotetrahydrofuran-2yl) ethyl 2-phenyl acetate. Both synthetic routes found to be applicable for many synthetic reactions. Introduction Angiopterlactones are diverse class of lactones integrated with ether linkage, which was isolated as metabolites from the plant Angiopteris caudatiformis by Zou and co-workers in 2009 and projected structures of angiopterlactone A 1, angiopterlactone B 2, along with osmundalctone 4, osmundalin 3 and 3–5 dihydroxy g-caprolactone 5. Authors did not demonstrated stereochemistry of lactone 3, 4 and 5 in isolation paper. [1] Among all these compounds only angiopterlactone A exhibits cytotoxic activity against HeLa cells, while osmundalactone and osmundalin shows insecticidal activity. [1] Indistinguishable lac- tone 1-(5-oxotetrahydrofuran-2yl) ethyl 2-phenyl acetate 6 was isolated from fungus Nigrospora sphaerica in 2009 by Pei and et al. [2] Angiopterlactone A 1 could be biosynthetic precursor of angiopterlactone B 2 which have unique structural features i.e tricyclic ring network pattern including two lactones, ether linkage, and seven adjacent stereocenters. Not long ago when our synthesis was in progress, the total syntheis has been reported by group of Bhattacharya applying intermolecular oxa- Michael addition of lactone 7 and 8. [3] We envisioned the same protocol of oxa-Michael addition for the synthesis of 2. To procure six-membered and five-membered lactone, we traced back our synthesis starting from ethyl l-lactate and ethyl propiolate which afforded propargylic ketone carbon skeleton, carbonyl functionality of ketone 14 was reduced using biocatalyst. After Mitsunobu reaction and Lindlar reduction we acquire five-membered a,b-unsaturated lactone 8. Hansen protocol of Z-selective semi-reduction was found most useful during synthesis of six-membered a,b-unsaturated lactone 7. In additional Scheme 2 lactone 6 could potentially be prepare by asymmetric dihydroxylation, Andos modified Wittig olefination, hydrogenation, and acid alcohol coupling reaction. To synthe- size new bioactive natural product in our research group, [11] [a] N. B. Khomane, Dr. J. S. Patel, P. K. Shirsat, P. R. Mali, Dr. H. M. Meshram Academy of Scientific and Innovative Research (AcSIR) New Delhi, India [b] N. B. Khomane, P.K. Shirsat, P. R. Mali, Dr. H. M. Meshram Medicinal Chemistry and Biotechnology Division CSIR-Indian Institute of Chemical Technology Tarnaka, Hyderabad-500007, India E-mail: hmmeshram@yahoo.com [c] Dr. J. S. Patel Natural Product Laboratory CSIR-Indian Institute of Chemical Technology Hyderabad-500 007, India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201703183 Scheme 1. Disconnection of angiopterlactone B Full Papers DOI: 10.1002/slct.201703183 1517 ChemistrySelect 2018, 3, 1517 – 1520  2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim