Comprehensive and Uniform Synthesis of All Naturally Occurring Phosphorylated Phosphatidylinositols

Abstract

Studies of cellular signal transduction mechanisms involving receptor-mediated generation of inositol phosphates and phosphorylated phosphatidylinositols require easy access to these naturally occurring products. Although numerous synthetic methods have been developed during the past decade, most of these methods suffer from excessive length and lack of generality. In this work we describe the comprehensive and uniform synthesis of all naturally occurring phosphatidylinositols such as phosphatidylinositol, phosphatidylinositol 3-phosphate, 4-phosphate, 5-phosphate, 3,4-bisphosphate, 3,5-bisphosphate, 4,5-bisphosphate, and 3,4,5-trisphosphate, featuring both saturated and unsaturated fatty acid chains.

Chemical Synthesis and Molecular Recognition of Phosphatase-Resistant Analogues of Phosphatidylinositol-3-phosphate

“…[35][36][37][38] The separation of diastereomeric derivatives of myo-inositol with chiral auxiliaries is also used in many synthetic routes. [39][40][41] In our early work, we developed the synthesis of enantiomerically-pure PtdInsP n and a variety of derivatives from D-glucose via the Ferrier rearrangement. 28,41 In this paper, we have employed the more atom-efficient production of the enantiomeric inositol derivatives via the resolution of myo-inositol by crystallization of diastereomeric D-camphor ketals.…”

“…28,41 In this paper, we have employed the more atom-efficient production of the enantiomeric inositol derivatives via the resolution of myo-inositol by crystallization of diastereomeric D-camphor ketals. 40 Each of the phosphorylated phosphatidylinositols synthesized in this work employed the simple and elegant protection scheme developed by Bruzik. 40 The inositol 1-position was silylated with the TBDPS group, the phosphomonoester 3-position was protected as a benzoate group, and all the remaining hydroxyl groups were protected as methoxymethyl (MOM)-ethers.…”

“…40 Each of the phosphorylated phosphatidylinositols synthesized in this work employed the simple and elegant protection scheme developed by Bruzik. 40 The inositol 1-position was silylated with the TBDPS group, the phosphomonoester 3-position was protected as a benzoate group, and all the remaining hydroxyl groups were protected as methoxymethyl (MOM)-ethers. In this way, 1-O-(tert-butyldiphenylsilyl)-2,4,5,6-O-tetrakis(methoxymethylene)-myo-inositol was synthesized from myo-inositol in six steps.…”

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…A suitable inositol precursor such as 255 was also sought that could be resolved and blocked with protective groups that could be introduced and removed as required and then phosphorylated and deprotected in a strategy loosely based upon the protecting groups previously employed elsewhere. [243] The protective groups employed were the acetal at the 2,3-positions (256) (cyclohexylidene was then replaced with a benzylidene derivative 257 on the Wang resin) and TBDPS (tertbutyldiphenylsilyl) was located at the 1-position. The less toxic MEM (methoxyethoxymethyl) and benzoyl protecting groups were also used at positions 4-, 5-and 6-in 257 to synthesise phosphatidylinositol analogues containing a short C-8 chain or aminopropyl derivative that made them water soluble.…”

Synthesis and Biological Activity of PTEN-Resistant Analogues of Phosphatidylinositol 3,4,5-Trisphosphate

“…21 DiC 16 -PtdIns(3,4,5)P 3 is an early mediator of the insulin-stimulated sodium transport in A6 cells. 19 Thus, we compared the effect of the unmodified diC 16 -PtdIns(3,4,5)P 3 with diC 16 -3-PT-PtdIns(3,4,5)P 3 1c and diC 16 -3-MPPtdIns(3,4,5)P 3 2c on sodium transport across confluent monolayers of A6 cells. As shown in Figure 1, apical addition of either 1c or 2c increased sodium transport.…”