De novo synthesis of the enantiomers Ins(1,2,3,4)P 4 and Ins(1,2,3,6)P 4 Ðregiospeci®city of their enzymatic dephosphorylation O. Plettenburg, S. Adelt, G. Vogel and H.-J. Altenbach* Institut fu Èr Organische Chemie und Biochemie, Bergische Universita Èt Wuppertal, Gaussstrasse 20, 42097 Wuppertal, Germany Received 22 December 1999; accepted 11 February 2000 Abstract The ®rst total synthesis of Ins(1,2,3,4)P 4 and Ins(1,2,3,6)P 4 is presented. Starting from p-benzoquinone, we took advantage of the C 2 -symmetry of conduritol-B intermediates. The target compounds were dephosphorylated by several enzymes, and the resulting InsP 3 isomers were identi®ed. Some of these enzymatic conversions were found to be preparatively applicable and to allow the synthesis of Ins(1,2,3)P 3 , Ins(2,3,6)P 3 and Ins(1,2,4)P 3 . # 2000 Elsevier Science Ltd. All rights reserved. Phytases (InsP 6 -phosphohydrolases) are enzymes capable of hydrolyzing phytic acid to yield phosphate and a series of lower phosphorylated inositols, ultimately in many cases free myo- inositol itself. Ins(1,2,3,4)P 4 1 1a and Ins(1,2,3,6)P 4 2 1b have each been identi®ed, along with other InsP 4 intermediates, as products of several phytases. In addition, either 1a or 1b has been detected in rat pancreatoma cells. 3 In the course of studies of the p42 IP4 receptor, 4 we obtained evidence that 1a or 1b occurs in rat brain tissues as well. These compounds may function physiologically as iron carriers 5 and calcium absorption enhancers. 6 We present here the ®rst total synthesis of the enantiomeric pair 1a and 1b (Fig. 1). 0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0957-4166(00)00063-X Tetrahedron: Asymmetry 11 (2000) 1057±1061 Figure 1. * Corresponding author. E-mail: orgchem@uni- wuppertal.de