Routine Use of Natural Abundance Deuterium NMR in a Polypeptidic Chiral Oriented Solvent for the Determination of the Enantiomeric Composition of Chiral Building Blocks Arnaud Parenty, † Jean-Marc Campagne,* ,† Christie Aroulanda, ‡ and Philippe Lesot* ,‡ ICSN-CNRS, AVenue de la Terrasse, 91198 Gif sur YVette, France, and Laboratoire de Chimie Structurale Organique, CNRS ESA 8074, ICMO, Ba ˆ t. 410, UniVersite ´ de Paris-Sud, 91405 Orsay, France philesot@icmo.u-psud.fr Received February 13, 2002 ABSTRACT Natural abundance deuterium 2D NMR spectroscopy in chiral liquid crystal was successfully used to efficiently analyze the enantiomeric composition of organic chiral building blocks involved in the syntheses of natural and synthetic bioactive products. The results reported here emphasize the high potential of this analytical strategy and prove its applicability for routinely determining enantiomeric excesses. Organic chiral building blocks play an essential role in the development of rapid and efficient syntheses of natural and synthetic bioactive products. In connection with an ongoing total synthesis project, we have identified 1 as a potential chiral building block for the synthesis of several natural products possessing interesting biological activities, such as lasiodiplodin, 1 dolatrienoic acid, 2 dehydrocurcuvalin, 3 macrolactines, 4 leukotrienes, 5 diplodialide A, 6 brefeldin A, 7 and mutolide 8 (Scheme 1). Synthesis of enantiomerically pure compound 1 from smaller chiral building blocks has been previously described but requires lengthy routes (from lactate 2a or glutamate 2b esters) or expensive starting material (chiral nonracemic propylene oxide 9 ). Alternatively, previ- ously described stoichiometric 10 or catalytic 11 asymmetric * To whom correspondence should be addressed. (for the synthetic part of this work: Email: Jean-Marc.Campagne@icsn.cnrs-gif.fr). ² ICSN-CNRS. ‡ Universite ´ de Paris-Sud. (1) Fuerstner, A.; Thiel, O. R.; Kindler, N.; Bartkowska, B. J. Org. Chem. 2000, 65, 7990-7995 and references therein. (2) (a) Duffield, J. J.; Pettit, G. R. J. Nat. Prod. 2001, 64, 472-479. (b) Moune ´, S.; Niel, G.; Busquet, M.; Eggleston, I.; Jouin, P. J. Org. Chem. 1997, 62, 3332-3339. (3) Liu, Y.; Li, Z.; Vederas, J. C. Tetrahedron 1998, 54, 15937-15958. (4) Jaruchoktaweechai, C.; Suwanborirux, K.; Tanasupawatt, S.; Kitta- koop, P.; Menasveta, P. J. Nat. Prod. 2000, 63, 984-986 and references therein. (5) Vidal, A.; Durand, T.; Vidal, J.-P.; Rossi, J.-C.; Ravasi, S.; Zarini, S.; Sala, A. Bioorg. Med. Chem. Lett. 2000, 10, 665-668. (6) Ireland, R. E.; Brown, F. R. J. Org. Chem. 1980, 45, 1868-1880. (7) Fox, B. M.; Vroman, J. A.; Fanwick, P. E.; Cushman, M. J. Med. Chem. 2001, 44, 3915-3924. (8) Bode, H. B.; Walker, M.; Zeeck, A. Eur. J. Org. Chem. 2000, 8, 1451-1456. (9) Millar, J. G.; Oehlschager, A. C. J. Org. Chem. 1984, 49, 2332- 2338. ORGANIC LETTERS 2002 Vol. 4, No. 10 1663-1666 10.1021/ol020038b CCC: $22.00 © 2002 American Chemical Society Published on Web 04/26/2002