Sensing Remote Chirality: Stereochemical Determination of β‐, γ‐, and δ‐Chiral Carboxylic Acids

Abstract

Determining the absolute stereochemisty of small molecules bearing remote nonfunctionalizable stereocenters is a challenging task. Presented is a solution in which appropriately substituted bis(porphyrin) tweezers are used. Complexation of a suitably derivatized β-, γ-, or δ-chiral carboxylic acid to the tweezer induces a predictable helicity of the bis(porphyrin), which is detected as a bisignate Cotton Effect (ECCD). The sign of the ECCD curve is correlated with the absolute stereochemistry of the substrate based on the derived working mnemonics in a predictable manner.

De novo synthesis, structural assignment and biological evaluation of pseudopaline, a metallophore produced by Pseudomonas aeruginosa

“…The second C–N bond formation between 13a and the protected L-His 13 was realized through the Mitsunobu reaction to afford the desired product 5a with the pseudopaline skeleton. However, the initial attempts for the one-step conversion to di-acid 14a with ruthenium trichloride19 a or ozonolysis19 b only gave complex mixtures. Gratifyingly, Lemieux–Johnson oxidation of 5a afforded dialdehyde,19 c which could be further oxidized to generate di-acid 14a without purification using the Jones reagent 16 a…”

Host–Guest Assembly of a Molecular Reporter with Chiral Cyanohydrins for Assignment of Absolute Stereochemistry

“…Molecules that have two sites of attachment are used directly with the porphyrin tweezer –. On the other hand, molecules with a single site of attachment require derivatization with a non‐chiral carrier that ultimately provides a second site for binding to the porphyrin tweezer ,,. In our present campaign with cyanohydrins, one could conclude that the molecule could fit both categories, depending on whether or not the cyano group is capable of functioning as the second site of attachment.…”

First Synthesis and Characterization of Stereoisomers of Choleretic Drug Dihydroxydibutylether

“…High resolution mass spectroscopy data of the product were collected on a Waters Micromass GCT or a Bruker Apex IV FTMS instrument. Methyl (R)-3-(benzyloxy)butanoate (2a) [13] To a stirred solution of methyl (R)-3-hydroxybutanoate 1a (2.57 g, 21.8 mmol) and benzyl trichloroacetimidate (5.00 g, 19.8 mol) in dichloromethane (20 mL) was added trifluoromethanesulfonic acid (0.30 g, 2.0 mmol) at room temperature. Stirring was continued for 24 h. The reaction was quenched by addition of saturated aqueous NaHCO 3 (20 mL), followed by the separation of the organic phase.…”

“…The oil was purified by silica gel column chromatography (petroleum ether/ethyl acetate 20∶1) to give 2a (3.30 g, 85%) as a clear oil. α −23.4} [13] ; 1 Methyl (S)-3-(benzyloxy)butanoate (2b) [14] The compound 2b was obtained following the same procedure as described above in the synthesis of 2a. Clear oil from 1b.…”