Determination of absolute configuration of 1,3‐diols by the modified Mosher's method using their di‐MTPA esters

Abstract

1,3-Diols are frequently involved in biologically important compounds and, therefore, determination of the stereochemistry of these structural elements, in particular those in acyclic systems, has been one of the focuses of attention in natural products chemistry. The modified Mosher's method, commonly used for the determination of the absolute configuration of secondary alcohols, was applied to determine the absolute configuration of 1,3-diols with their di-MTPA esters. Several epimeric pairs of syn- and anti-1,3-diols with known absolute configurations were converted to the corresponding di-MTPA esters and the iDelta;delta values were then calculated. For the acyclic syn-1,3-diols, the iDelta;delta values were systematically arranged as predicted from the basic concept of the modified Mosher's method, demonstrating that the method is valid for these compounds. In contrast, the iDelta;delta values were irregularly arranged for the acyclic anti-1,3-diols and, accordingly, this method is not valid for these cases. These results are complementary to those of the previously reported CD exciton chirality method and, hence, the combined use of the modified Mosher's method and the CD exciton chirality method can determine the absolute configuration of the acyclic 1,3-diols. Also, this method is successfully applicable to cyclic 1,3-diols irrespective of their relative stereochemistry.

Nomimicin, a new spirotetronate-class polyketide from an actinomycete of the genus Actinomadura

“…These data allowed assignment of both the absolute configurations at C-7 and C-9 as R. Although signs were mixed for the protons flanked by the MTPA ester groups, the sign distribution pattern is in good accordance with that reported for bisMTPA derivatives of cyclohexane-1,3-diols. 12 The deduced absolute configuration was identical with that known for this antibiotic family. 13,14 Spirotetronates represented by kijanimicin 15 feature a trans-D 1 -octalin unit and a tetronic acid moiety spiro-linked with a cyclohexene ring.…”

2,2-Functionalized analogues of 1α,25-dihydroxyvitamin D3, the potent inducers of cell differentiation

“…The absolute stereochemistry of the diols in the A-ring was determined by 1 H NMR analyses of their bis-MTPA esters (Fig. 2) [13]. In this way, syntheses of two sets of four stereoisomers of 2,2-dimethyl-1,25-dihydroxyvitamin D 3 and 2,2-ethano-1,25-dihydroxyvitamin D 3 were accomplished.…”

Assignment of absolute configuration using chiral reagents and NMR spectroscopy

“…73 The bis-MTPA esters of model acyclic and cyclic 1,3-diols with syn-and anti-configurations show trends in most cases that can be used to assign the absolute configuration. 74 For acyclic 1,3-diols, the Dd RS are irregular, and it is recommended that NMR data be used in conjunction with the circular dichroism exciton chirality method. 75 The configuration of 1,2,3-primary,secondary,secondary-triols can be assigned using tris-MPA esters.…”