www.elsevier.nl/locate/carres Carbohydrate Research 328 (2000) 459 – 466 Total synthesis of the natural antigen involved in the hyperacute rejection response to xenotransplants  Christian Gege a , Willy Kinzy b , Richard R. Schmidt a, * a Faculty of Chemistry, Uniersity of Konstanz, Box M725, D -78457 Konstanz, Germany b Transplantation Research, NOVARTIS Pharma AG, S -507.701, CH -4002 Basel, Switzerland Received 15 February 2000; accepted 4 May 2000 Abstract The major glycosphingolipid in pig vascular endothelium is the ceramide pentasaccharide Gal(1 3)Gal(1  4)GlcNAc(1 3)Gal(1 4)Glc(1 0)Cer (1), which binds specifically to human anti-Gal antibody and is involved in the hyperacute rejection response in xenotransplantation from pig to man. The synthesis of 1 and its methyl glycoside 2 is described. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Synthesis; O-Glycosylation; -Galactosyl epitopes; Xenotransplantation; Glycosphingolipid; Ceramide 1. Introduction Human allotransplantation is nowadays a generally accepted treatment of choice for sev- eral illnesses. The major hindrance towards widened indications of organ transplantation as the preferred treatment, is the shortage of donor organs suitable for such clinical appli- cation. Xenotransplantation, i.e., transplanta- tion of tissue between different species, is considered one promising possible solution. The main problem in xenografting between discordant species however is the hyperacute rejection (HAR) of xenotransplants, which re- sults in the destruction of the vascular en- dothelium of the donor organ within minutes [1]. Man differs from other mammals in the expression of -galactosyl epitopes. These epi- topes are carbohydrate structures bearing an Gal(1  3)Gal terminus (-Gal epitopes). All human sera contain a large amount of natu- rally occurring antibody (anti-Gal), which binds to -Gal epitopes. These antigens are established as major xenoantigens on pig en- dothelium and are responsible for initiating the HAR of pig organs by humans and are thus of primary interest in the development of xenotransplantation. The major glycosphin- golipid in pig vascular endothelium is the ce- ramide pentasaccharide Gal(1  3)Gal(1  4)GlcNAc(1  3)Gal(1  4)Glc(1  0)Cer (1), which binds specifically to human anti- Gal antibody [2].  Presented at the 37th IUPAC-Kongress, Berlin/Germany, 14.-19.8.1999, SYN-1-128. * Corresponding author. Tel.: +49-7531-882538; fax: + 49-7531-883135. E -mail address: rrs@chclu.chemie.uni-konstanz.de (R.R. Schmidt). 0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII:S0008-6215(00)00145-2