Pergamon Bioorganic & Medicinal Chemisoy Letters, Vol.7, No. 17, pp. 2251-2254, 1997 © 1997Elsevier Science Ltd All rightsreserved. Printedin GreatBritain 0960-894X/97 $17.00+ 0.00 PII: S0960-894X(97)0041 O- 1 THE EFFICIENT SYNTHESIS OF A BIS-GLYCOSYLATED STEROID DRUG TRANSPORT REAGENT: METHYL 3-13-AMINO-7~, 12~t-DI(I'ct-GLUCOSYL)-513- CHOLATE (TC002) Michael J. Sofia*, Ramesh Kakarla, Natan Kogan, Richard Dulina, Y.W. Hui, Nicole T. Hatzenbuhler, Dashan Liu, Anna Chen, and Thomas Wagler Transcell Technologies htc., 8 ( 'edar Brook Drive, (7ranbury, NJ 08512 Abstract: The drug transport reagent, methyl 3-13-amino-7ot, 12a-di(l'a-glucosyl)-513-cholate (TC002) 1 was prepared in 15% overall yield from pentaacetyl glucose and methyl cholate Pentaacetyl glucose was converted to glucosyl sulfoxide 2 in 56% overall yield. Methyl cholate was converted to methyl 3-13-azido cholate 3 in 67% yield. Bis-glycosylation of 3 with 2 followed by a single step reduction provided 1. © 1997 ElsevierScienceLtd. The development of both nontraditional drugs, such as peptides, proteins and oligonucleotides and many hydrophilic small molecule drugs has been hampered because of their inability to pass through membrane barriers. Recently, the discovery that facially amphiphilic glycosylated steroids facilitate the transport of both nontraditional drugs and hydrophilic small molecules drugs across membrane barriers has led to the development of methyl 3-13-amino-7a, 12~-di(l'~-glucosyl)-513-cholate (TC002) as a general drug delivery reagent (Figure 1) ~ In our efforts to develop TC002 for clinical applications, we required an efficient large scale synthesis of this bis-glycosylated steroid. In this report, we describe an efficient large scale synthesis of TC002 thus making this material accessible for clinical study. C7 oc.3 /I } ?oH OH 1 (TC002) Figure 1 2251