Mosher ester method

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 stereochemistry of each enantiomer separated by the chiral HPLC has been studied after methanolysis of the epoxy ring. Examining the H NMR data of esters of the produced methoxyalcohols with (S)- and (R)-a-methoxy-a-(tri-fluoromethyl) phenylacetic acid by a modified Mosher s method [181], it has been indicated that the earlier eluting parent epoxides are (3S,4R)-, (6S,7R)-, and (9R,10S)-isomers (Table 7) [75, 76, 179]. The above three chiral HPLC columns show different resolution abilities but a different elution order is not observed. The resolution profile by the reversed-phase OJ-R column has been generalized with molecular shapes of the epoxy compounds considering the... 

The result of this method is consistent with that obtained by using the corresponding Mosher s ester method (Adn = d(/o-ATMA - (s)-atma) (Fig- 1-25). Note that in the method of Mosher s ester, (Ss — Sr) was applied to calculate Ah) i, the difference in the 2ATMA method is only due to the configuration nomenclature difference caused by the CIP rule. 

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. 

The synthesis was achieved from commercially available (+)-2, 3-0-isopropylidene-L-threitol in 26 steps. The key steps are the stereoselective construction of a chloroolefin unit [step f in Scheme (2)] and the intramolecular Reformatsky-type reaction [step g in Scheme (3)]. Because the stereochemistry of C3, Cll, C13 and C14 in synthetic 8 was undoubtedly constructed to be all S by the organic synthetic method, the absolute stereochemistries of C3, Cll, Cl3 and C14 in natural 2 were determined to be R, R, R and R. On the other hand, since the absolute stereochemistry of CIS in natural 2 was determined to be R by the modified Mosher s method, the total absolute stereochemistry of haterumalide NA (2) was revealed, which revised the previously reported structure [8]. To confirm these results, 8 was converted into the (i )-MTPA ester, which was the enantiomer of the (5)-MTPA ester of the natural haterumalide NA methylester on comparison of their H NMR spectra. 

Since zamamistatin (17) was an optically active alcohol with a C2 symmetrical structure, the absolute stereochemistry was determined using the modified Mosher s method [7]. The diol 17 was transformed into the (R)- and (iS)-MTPA esters. The calculated values ppm)... 

The absolute stereochemistry of 20 was determined using the modified Mosher s method [7]. Reduction of 20 with LiAlELt followed by TBDPSCl (tert-butyldiphenylsilyl chloride)/imidazole gave TBDPS ether 20A, Fig. (16). Treatment of 20A with (K)- and (5)-MTPACl gave (R)-and (5)-MTPA esters, 20B and 20C, respectively. The results, as shown in Fig. (16), established that the configuration at C3 was 35. Therefore, the absolute stereochemistry of haterumadioxin A (20) was determined to be 35, 6R and 8i . 

Amphidinolide Q (16), C21H34O4, is a 12-membered macrolide possessing four branched methyl groups, an a ti-methylene, and a ketone carbonyl, isolated from the marine dinoflagellate Amphidinium sp. (strain Y-5). The relative stereochemistry of amphidinolide Q (l) was elucidated on the basis of -based configuration analysis method and NOESY correlations. The absolute configurations of amphidinolide (16) were concluded to he AR, 7R, 9S, 115, and 135 by application of the modified Mosher s method to amphidinolide 0 (16) and the linear methyl ester derivatives of amphidinolide... 

INADEQUATE spectrum. The absolute configurations at C-11, C-12, and C-14 were elucidated by combination of the y-based configuration analysis and the modified Mosher s method. Originally, the absolute configuration at C-6 was proposed to be S on the basis of H NMR data of 6,11,12-rm-MTPA esters of C-... 

Isobutyl lactate Enzymatic method GC on CSP LC on CSP GC on Mosher esters... 

In conclusion, two points must be emphasized. First, the rationales presented in Figures 2.5 and 2.6 are only models, and do not necessarily represent preferred conformations. Second, it should be restated that in order for the CDA method to be accurate, any adventitious kinetic resolution in the derivatization must be quantitated or eliminated. For example, Heathcock has noted that MTPA derivatization of a racemic alcohol (0% ee) afforded a 1.7 1 mixture of Mosher esters (26% de) and the % ee determinations had to be corrected accordingly [42]. More recently, Svatos used a five-fold excess to force a derivatization to completion [43]. If the appropriate control experiments are done, derivatization with Mosher s reagent can be a very reliable method for determination of enantiomer ratios and absolute configuration of amines and alcohols. For the derivatization of ketones, chiral diols may be used [44], but similar control experiments should be undertaken. 

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