Biotine methyl ester

It has already been demonstrated that xenon difluoride reacts with various phenyl-substituted products52-54. The strategy has been further explored by Janzen and coworkers for fluorination of thioamino acids55,56, while reaction with (d-)biotin methyl ester gives two monofluoro products57 in acetonitrile at 5-10 °C (Scheme 13). 

Methyl 4,6-0-benzylidene-3-deoxy-a-D-ribo-hexopyranoside (56) was benzoylated, debenzylidenated, and partially p-toluenesulfon-ylated to 57 this was converted into 58 by reaction with sodium iodide, followed by catalytic reduction. The methanesulfonate of 58 was converted into 59 by reaction with sodium azide in N,N-dimethylformamide, and 59 was converted into 4-azido-3,4,6-trideoxy-a-D-xylo-hexose (60) by acetolysis followed by alkaline hydrolysis. Reduction of 60 with borohydride in methanol afforded 61, which was converted into 62 by successive condensation with acetone, meth-anesulfonylation, and azide exchange. The 4,5-diazido-3,4,5,6-tetra-deoxy-l,2-0-isopropylidene-L-ara/uno-hexitol (62) was reduced with hydrogen in the presence of Raney nickel, the resultant diamine was treated with phosgene in the presence of sodium carbonate, and the product was hydrolyzed under acidic conditions to give 63. The overall yield of 63 from 56 was 4%. The next three reactions (with sodium periodate, the Wittig reaction, and catalytic reduction) were performed without characterization of the intermediate products, and gave (+)-dethiobiotin methyl ester indistinguishable from an authentic sample thereof prepared from (+)-biotin methyl ester. 

Considering the previous remarks, the use of these techniques remains interesting, even in the case of complex molecules, e.g., the interpretation of the biotin methyl ester spectrum [128] (Fig. 20). 

This analytical mode has a resolution sufficient for the fragment ions. For instance, the B/E linked scan spectrum of the unimolecular decomposition of the MH ion (m/z 259) of biotin methyl ester, produced by Cl ammonia, has a good resolution (< 1 u). The m/z 221, 241 and 243 ions are due to the elimination of neutral fragments (CH3OH, HjO and CH4), which characterize Cl mass spectra (Fig. 21). 

Figure 21. B/E linked scan spectra of MH ions produced from biotin methyl ester under CI/NH4 conditions.

Figure 11. B jE linked scan sp dra of m/z 198 (a), m/z 185 (b) and m/z 166 (c) ions produced by decomposition of biotin methyl ester in the source under El conditions.

Figure 38. Analysis by MIKE/CAD mode of ion m/z 259 (MH ) produced from an authentic sample of biotin methyl ester (in CI/NH4) (a) and from the unknown mixture (b).

Biotin methyl ester Fluorophore-labelled probes Biotin nitrophenyl ester MeCN Biotin methyl ester [58]... 

A biomimetic synthesis of (+)-biotin methyl ester (665), involving stereospecific ring-closure to a tetrahydrothiophen system during the final stage, is shown in... 

In 1940 Gyorgy, Du Vigneaud and co-workers obtained pure vitamin H ester from liver concentrates. The similar biological properties led them to assume that their product was identical with Kogl s biotin methyl ester. The free vitamin prepared from the methyl ester by the American group had the composition CioHi60sN2S and formed colorless needles melting at 230-232° ([ ]d = +92°, 0.3% in o.i N NaOH). 

Desthiobiotin was first prepared as the methyl ester by removal of sulfur from biotin methyl ester with Raney nickel and also from biotin by the same method . It is microbiologically as active as biotin. The racemic compound was synthesized by three groups almost simultaneously. Wood and Du Vigneaud published the first synthesis (Fig. 5). Bourquin, Schnider and Griissner prepared in a somewhat simpler manner the intermediate... 

Now that we have examined objectively three mechanisms that agree with the experimental results, we should examine the real problem in biotin chemistry. Indeed, in recent years a controversy has arisen regarding the exact site on biotin to which the carboxyl group is attached. During isolation and characterization by Lynen of the relatively unstable free carboxybiotin, particularly at acidic pH, the product was converted to the more stable dimethyl ester with diazomethane (343, 344). This derivative was subsequently identified as r-N-methoxycarbonyl-( + )-biotin methyl ester. The same product was also obtained by enzymatic degradation of enzyme-bound biotin. Figure 7.16 shows some of these transformations. 

Although many transition metals are known to promote oxidative carbonylation of amines to ureas, only palladium- and wolfram-catalyzed processes were used in the synthesis of compounds of pharmaceutical importance. Urea 46, a potent antagonist of the neuropeptide Y5 receptor was obtained starting from 9-isopropyl-4-methyl-9H-carbazol-3-ylamine and morpholine, using the Pdl2/KI catalyst under 20 bar of 4/1 carbon monoxide/air mixture [62], Intramolecular versions of this reaction were carried out vrith another system, using W(CO)6 as the catalyst and I2 as the oxidant during the synthesis of biotin methyl ester 47 [63], and the core structure of the HIV protease inhibitors 48 and 49 [64]. 

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