Mosher ester absolute configuration

The absolute configuration of 215a, initially assigned through Mosher ester experiments, was later revised by De Brabander (a) Wu Y, Esser L, De Brabander JK (2000) Angew Chem Int Ed 39 4308 (b) Wu Y, Seguil OR, De Brabander JK (2000) Org Lett 2 4241... 

Absolute configurations were ascribed on the basis of an empirical model by analogy to l-hydroxyaUcanephosphonates. They are opposite to those obtained from the NMR spectra of the Mosher s esters of 2-hydroxyalkanephosphonates (entries 4-6) and whose absolute configuration is known. / -Chlorophenyl acetate was used as the acetylating agent. 

Investigations on the stereochemistry of chiral semiochemicals may be carried out by (gas) chromatographic separation of stereoisomers using chiral stationary phases, e.g. modified cyclodextrins [32]. Alter natively, formation of diastereomers (e.g. Mosher s ester or derivatives involving lactic acid etc.) may be followed by separation on conventional achiral stationary phases. Assignment of the absolute configuration of the natural product will again need comparison with an authentic (synthetic) reference sample. 

Tbe compounds were characterized throughout detailed spectroscopic, spectrometric and chemical analyses. The absolute configuration at the stereogenic centers in compounds 4, 5, 12 and 16 was established by applying the Mosher ester methodology. Furthermore, the structures of coumarins 4, 5 and 10 were confirmed by X-ray analysis. 

In toluene with 4 equiv methanol and a catalytic amount of the alkaloid. b ee values are determined by conversion of the monoesters to the (R)-l-(l-naphthalenyl)ethylamides (entries 1-14) and analysis by HPLC, by salt formation with (R)-l-phenylethylamine (entries 15-20) or by H-NMR spectroscopy in the presence of Eu(hfc)3. Absolute configurations are determined by chemical correlation or by X-ray analysis of the Mosher ester of the lactone alcohol (entry 21). With 20 equiv of methanol. d With 4 equiv of methanol. With 10 equiv of methanol. f With 3 equiv of methanol. 

Absolute configuration is derived by chemical correlation and ee values are based on conversion to the Mosher ester and H-NMR spectroscopy. b From Fluka. 

In order to determine the absolute configuration or the enantiomeric excess of a compound containing a hydroxy group, it is often esterified with a pure enantiomer of Mosher s acid (3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid, MTPA). Which configuration has the ester derived from (S)-l-phenyl-propan-l-ol and (R)-Mosher s acid chloride ... 

Interestingly, hydrolase-type enzymes could also be employed for enantioselective hydrations79. Yields and enantiomeric excess values obtained in the addition of water to 2-(trifluo-romethyl)propenoic acid (7) are summarized. Unfortunately, the absolute configuration of the product 8 was not determined, the enantiomeric excess values stated rest on 19F-NMR analysis of the Mosher ester. Whereas ethanol and phenol did not react under these conditions, the /V-nucleophiles diethylamine and aniline, and also thiophenol, could be added to 7 in moderate to good yields and enantiomeric excess values. Finally, the bifunctional aniline derivatives 9 afforded the lactams 10 in 52-90% yield and 25-67% ee. Again, the absolute configurations of the products were not determined. 

Synthesis of 15,16,19,20,23,24-/>exep/-uvaricin (a diastereomer of the natural product) confirms relative configuration and establishes absolute configuration (via Mosher esters) of the first acetogenin, uvaricin. 

Absolute configuration of C(4) in C(4)-hydroxylated compounds determined by NMR analysis of Mosher ester derivatives and comparison to model compounds. All configurations studied determined to be R at C(4). Method also applicable for determining the relative configuration between C(4) and C(36), as well as the absolute configurations of carbinol centers adjacent to THF rings. 

Figure 15. Absolute Configuration of the A2 Subunit in Builatacin (5), Asimicin (13), Rolliniastatin 1 (8), Annonacin (3), and Annonacin-10-one (26) Is (4R,36S) [or (4f ,34S) for 3 and 26] from Comparison of their Mosher Esters with Those of Synthetic Modei Compounds 28.

In another experiment, annonadn (3) was oxidatively cleaved with mCPBA to muricatacin (38) (Figure 21), the absolute configuration of which had been established by optical rotation. This conversion suggested the /7 configuration at C(20) of annonacin. This fact was later borne out by the Mosher ester method described earlier in this chapter, lending support to the validity of the method. 

The tetrahydrophenanthrene derivative, (l,l,7,8-tetramethyl-l,2,3,4-tetrahydrophenanthrene, 432), has been isolated from a 180 Ma old marine sedimentary rock [198]. Heliophenanthrone (434) was isolated from the aerial parts of Heliotropium ovalifolium. Its structure was elucidated on the basis of spectroscopic data, and the absolute configuration of the asymmetric centers was determined from LC-NMR data of the Mosher ester derivatives [199]. The structure of domohinone (436) from Domohinea perrieri Leandri was confirmed by single-crystal... 

The magnetic anisotropy effect of chiral MaNP acid is much stronger than that of conventional chiral carboxyUc acid (Fig. 9.13). For instance, the Ad values of the MaNP-menfhol ester are ca. four times larger than those of Mosher s MTPA ester [13] (Fig. 9.13b) twice fhe value for Trosfs MPA ester [15] (Fig. 9.13c) comparable to 1-NMA and 2-NMA esters reported by Riguera [14] and Kusumi et al. [12]. MaNP acid is fhus effective for determining the absolute configuration of natural products. 

The first total synthesis of 112, from 6-chloronicotinaldehyde, confirmed the structure of the alkaloid [323]. There have been many subsequent syntheses of 112 and analogs. In one recent synthesis [324], (+)- and (-)-U2 were prepared after resolution of an intermediate via formation of a Mosher s ester. X-ray crystallography established the absolute configuration of the ester formed from (/ )-(-)-Mosher s acid as 15, 25. This ester ultimately produced (-)-112, the unnatural enantiomer. Thus, the absolute configuration of the natural product was determined to be 1R, 2R, 45 [324]. 

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