Catalytic Antibodies in Synthesis:  Design and Synthesis of a Hapten for Application to the Preparation of a Scalemic Pyrrolidine Ring Synthon for Ptilomycalin A

Abstract

A catalytic antibody-based approach toward the synthesis of an optically active pyrrolidine ring synthon potentially useful for ptilomycalin A is described. Enantiomerically pure hapten 37 was designed and constructed with the eventual goal of generating antibodies for the enantioselective partial hydrolysis of a meso diester such as 44 into a monoacid 45. This transition state analog possesses a phosphonate group containing the requisite oxyanionic character of the tetrahedral intermediate for ester hydrolysis. A newly developed carbamate-based linker, which was found to be much more hydrolytically stable than the commonly used glutarate ester, was developed for coupling of the hapten to a carrier protein.

Investigations on New Strategies for the Facile Synthesis of Polyfunctionalized Phosphinates: Phosphinopeptide Analogues of Glutathionylspermidine

“…The resultant ethyl ester 15 also failed to react with 9b under Michaelis−Becker conditions. Similar problems have been encountered using the Michaelis−Becker reaction for the synthesis of complex phosphonates 2 …”

Artificial Organic Host Molecules for Anions

“…The guanidinium group as present in the side chain of arginine is ubiquitous in enzymes that bind anionic substrates and is also involved in the stabilization of protein tertiary structures via internal salt bridges with carboxylate functions. The reason for the strong interaction with oxoanions lies in the peculiar binding pattern featuring two parallel hydrogen bonds in addition to the electrostatic attraction (Figure ), a structural motif that can be found in many crystal structures of enzyme complexes with oxoanionic substrates as well as in simple guanidinium salts. , This type of binding appears to form also the basis for the biological activity of quite a number of alkaloids and toxins such as ptilomycalin A and related guanidinium natural products. ,,

5 Binding pattern of guanidinium groups with oxoanions found in many X-ray structures of the corresponding salts.

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“…254,255 This type of binding appears to form also the basis for the biological activity of quite a number of alkaloids and toxins such as ptilomycalin A and related guanidinium natural products. 63,256,257 Another feature which makes the guanidinium moiety an attractive anchor group in artificial receptors 258 is the extremely high basicity of guanidine (pK a ) 13.5), which guarantees protonation over a wide pH range. On the other hand, the exploitation in host-guest chemistry is hampered by the very effective solvation of the guanidinium function in water along with the lower charge density as compared to that of ammonium-based receptors, leading to weaker electrostatic interactions.…”

Convergent Synthesis of Glycodendropeptides by Click Chemistry Approaches

“…Trispropargyl alcohol 15 12 was prepared from commercially available pentaerythritol in good yield. Using its free hydroxy group, a short spacer was introduced by reaction with acid 16 ,13 obtained in one step from succinic anhydride and 2‐bromoethanol 14. Coupling of compounds 15 and 16 was mediated by dicyclohexylcarbodiimide (DCC) and dimethylaminopyridinium p ‐toluenesulfonate (DPTS) at room temperature, affording compound 17 in moderate yield (40 %) though the efficiency of this coupling could be substantially improved (to ~ 80 %) by heating at 40 °C.…”