Synthesis and Analysis of the All-(S) Side Chain of Phosphomycoketides: A Test of NMR Predictions for Saturated Oligoisoprenoid Stereoisomers

Abstract

(4S,8S,12S,16S,20S)-Pentamethylheptacosan-1-ol has been synthesized and analyzed by resolution-enhanced NMR spectroscopy with the aid of a recent set predicted spectra of all its stereoisomers. The configuration was confirmed but isomer purity of the sample (~70%) was lower than expected. A truncated analog, (2S,6S,10S,14S)-2,6,10,14-tetramethylhenicosan-1-ol TBDPS ether, was prepared from a late stage synthetic intermediate. Analysis of its spectra confirmed the configuration and showed that the sample was isomerically pure. The results suggest that a late-stage epimerization, not a failure of an asymmetric synthesis step, caused the formation of minor stereoisomers in the sample of pentamethylheptacosan-1-ol. The study shows the value of the predicted set of oligoisoprenoid spectra and further extends the predictive model to a new subclass of compounds.

Lipids of Clinically Significant Mycobacteria

“…26) (Matsunaga et al 2004;Quadri 2014). The structures of these mannosyl phosphomycoketides (MPMs) were confirmed by synthesis (van Summeren et al 2006;Scharf et al 2010;Buter et al 2013).…”

A Practical and Stereoselective Organocatalytic Alkylation of Aldehydes with Benzodithiolylium Tetrafluoroborate

“…Recently, Minnaard described the total synthesis of a deoxypropionate chain used in the study of new antibiotics for Gram‐negative bacteria . Sufficient quantities of the desired products are required to establish the relative and absolute configuration of many kinds of these natural products, as their structure is still not known or not completely assigned . We want to establish the absolute and relative configuration of the methyl groups in the deoxypropionate chains, using our relatively straightforward alkylation strategy.…”

“…53 Sufficient quantities of the desired products are required to establish the relative and absolute configuration of many kinds of these natural products, as their structure is still not known or not completely assigned. 54 We want to establish the absolute and relative configuration of the methyl groups in the deoxypropionate chains, using our relatively straightforward alkylation strategy. Contrary to the chemistry previously described by others, we make use of commercially available catalysts and precursors with mild reaction conditions.…”

Short Stereoselective Synthesis of the Phytophthora Universal Mating Hormone α1 Using Lithiation/Borylation Reactions

“…[15] Protection of the tertiary alcohol with TESCl gave the carbamate 15, our precursor for the second and final lithiation/borylation reaction. However, under the standard reaction conditions (Et 2 O, TMEDA, sBuLi, À78 8C, 5 h) we obtained a complex mixture of products.…”