New Dendrimers and Lipids Based on 2,2′-Bi(glycerol), and Lewis Acid Dependent Rearrangements of a Protected Pinacol

Abstract

Chapter 1: 2,2'-Bi(glycerol), or 2,3-bis(hydroxymethyl)butane-1,2,3,4-tetraol is of interest because of its utility as a potential A6 core for novel dendrimers, and because it may lead to hitherto un¬known 2,2'-bi(triglyceride)s and 2,2'-bi(phosphodiglyceride)s. It may also serve as a starting point for the preparation of unnatural sugars. Previous work in our group established a workable synthesis of 2,2'-bi(glycerol), however a shorter route was desirable. We examined alternate routes to 2,2'-bi(glycerol) and found all suffered from unexpected cleavage of the central C-C bond. Chapter 2: We envisioned new dendrimers based on 2,2'-bi(glycerol) functioning as an A6 core. A convergent synthetic plan called for Rh2(OAc)4 catalyzed insertion of the carbenoid derived from dimethyl 2-diazomalonate into both O-H bonds of malonic acid, giving di-[bis(methoxycar-bonyl)methyl] malonate. Diazotization of the central CH2 would then enable a new insertion into malonic acid. We found that all traditional diazo transfer protocols failed for di-[bis(methoxycar-bonyl)methyl] malonate. The reasons for this failure were investigated at length. We found that simple base treatment of the tetraester malonate may have resulted in acylketene formation. Chapter 3: In the course of synthesis of 2,2'-bi(triglycerides), we studied the acylation of 5,5'-bi(5-hydroxy-2,2-dimethyl-1,3-dioxane) under basic and Lewis acidic conditions. All Lewis acid cata¬lysts investigated in this work caused skeletal rearrangements, leading to 4,4'-bi(4-acetoxymethyl-2,2-dimethyl-1,3-dioxolane), or 4,4,5,5,-tetra(acetoxymethyl)-2,2-dimethyl-1,3-dioxolane. Reaction intermediates, for example 2,2,8,8,13,13-hexamethyl-1,3,7,9,12,14-hexaoxa-dispiro[4.5.4.0]pentadecane, were also identified.