@article{db656fcd6a55452e8b8e4d14ceadfb2c,
title = "Synthetic studies on azadirachtin: Construction of the highly functionalized decalin moiety of azadirachtin",
abstract = "Construction of the left segment of azadirachtin in naturally occurring enantiomer is described. The key reaction is an intramolecular Diels-Alder reaction, which was performed under thermal conditions to afford the highly functionalized decalin compounds selectively.",
keywords = "Azadirachtin, Decalin, Diels-Alder reaction",
author = "Jun Ishihara and Yuuko Yamamoto and Naoki Kanoh and Akio Murai",
note = "Funding Information: reaction proceeded to give compounds 24a and 24b, along with recovery of 23 (Table 1). When the thermal treatment for 60 h in the presence of BHT was carried out, decalin compounds 24a and 241) were obtained in 12% and 31% yield, respectively (entry 3). Interestingly, no other tricyclic products could be detected in any cases. The structures of the two adducts were determined on the basis of tH-, '3C-NMR, DQFCOSY, HSQC, HMBS, and NOESY spectra. 24b was also identified by X-ray crystallography. Both products were found to be the desired trans-decalicno mpounds, and each was the diastereoisomer at C-8. It should be noted that the longer reaction time increased the yield of compound 24b. It is plausible that compound 24b would be produced by the isomerization of 24a. In fact, the MM2 calculation indicated that the energy of 241) was 1.5 kcal/mol lower than that of 24a. Exclusive formation of the trans-decalinco mpounds in the IMDA of 23 would be attributed to the following steric effects: that is, i) the chair conformation would be preferential in the transition state in order to be fixed by the cyclic carbonate; ii) existence of a severe non-bonding interaction between the acetonide group and diene, and the N'3-strain of butenolide would be reponsible for the resultant facial selectivity. Both tricyclic products could be the versatile intermediates of the further coupling reaction with the fight segment of 1. The desired tricyclic intermediates of azadirachtin were thus prepared in 18 steps from ethyl malonate via a thermal intramolecular Diels-Alder reaction. Further synthetic study is now under way in our laboratory. Acknowledgment: This work was financially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan (09780516, J.I.). We thank Prof. T. Inabe at Hokkaido University for permission to use X-ray diffractometer.",
year = "1999",
month = jun,
day = "4",
doi = "10.1016/S0040-4039(99)00755-8",
language = "English",
volume = "40",
pages = "4387--4390",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Limited",
number = "23",
}