Mesylates, synthesis, methanesulfonyl

Fig. 2. Synthesis of clinically useful monobactams where R = H, CH P is an amino protecting group, and Mes = mesyl is methanesulfonyl.

Our first synthesis of brassinolide started from stigmasterol which was converted to (20S)-6p-methoxy-3a,5-cyclo-5a-pregnane-20-carboxaldehyde (2). This pathway involved formation of the mesylate with methanesulfonyl chloride in pyridine and tetrahydrofuran, treatment of the mesylate with potassium acetate in methanol, and ozonolysis of die i-sterol with reductive work-up. 

One of the first compounds to be introduced to the clinic, aztreonam (40-9), has been produced by total synthesis. Constmction of the chiral azetidone starts with amide formation of L-threonine (40-1) via its acid chloride treatment with ammonia leads to the corresponding amide (40-2). The primary amino group in that product is then protected as its carbobenzyloxy derivative (40-3). Reaction of that product with methanesulfonyl chloride affords the mesylate (40-4). Treatment of that intermediate with the pyridine sulfur trioxide complex leads to the formation of the A -sulfonated amide (40-5). Potassium bicarbonate is sufficiently basic to ionize the very acidic proton on the amide the resulting anion then displaces the adjacent mesylate to form the desired azetidone the product is isolated as its tetrabutyl ammonium salt (40-6). Catalytic hydrogenation over palladium removes the carbobenzyloxy protecting group to afford the free primary amine (40-7). The... 

The same general scheme for introducing the 9a-fluoro substituent is applicable to corticoids that feature a 6a-methyl group. 6a-Methylprednisolone (9-4) provides the starting material for the synthesis of fluorometholone (23-5) (Scheme 7.23). The standard sequence is again used to introduce the 9a-fluoro function (9-4 23-1). The only readily accessible hydroxyl at C21 is next converted to the mesylate 23-3 by acylation with methanesulfonyl chloride. Treatment of that intermediate with sodium iodide replaces the mesylate to afford the more readily reducible 21-iodo... 

The structure of CCLXXXII was confirmed by an alternate synthesis. Pyrobikhaconitine (CCLXXI) was converted to dihydropyrobikhaconi-tine (CCLXXXV) by catalytic hydrogenation followed by reaction with methanesulfonyl chloride. The resulting dihydropyrobikhaconitine mesylate was identical with CCLXXXII produced by the high-pressure hydrogenation. 

The successful synthesis of the novel 2(S)-mercapto-Y-butyrolactone (19) is shown in Figure 7. This synthesis starts with 2(R)-hydroxy-Y-butyrolactone (16) which is conunercially available or may be conveniently prepared ftom d-malic acid 15). Conversion of 2(R)-hydroxy-Y-butyrolactone (16) to the corresponding crystalline 2(R)-mesylate 17, was accomplished by treatment with methanesulfonyl chloride in the presence of DMAP in EtOAc. The mesylate could be isolated by crystallization from the reaction mixture after work-up. Fortunately, a remarkable enantiomeric purification occurred during this... 

The azidomethyl-EDOT synthesis also starts from EDOT-CH2OH. The mesylate obtained with methanesulfonyl chloride can be reacted with sodium azide to azidomethyl-EDOT (see Figure 12.13). Decomposition to the corresponding amine (aminomethyl-EDOT) under evolution of nitrogen can be performed successfully with triphenylphosphane. The amine forms cyclic amides with, for example, naphthalenetetracarboxylic anhydride. 3... 

Methanesulfonates. The most common use of methanesulfonyl chloride is for the synthesis of sulfonate esters from alcohols. This can be readily accomplished by treatment of an alcohol with mesyl chloride in the presence of a base (usually Triethy-lamine or Pyridine). The methanesulfonates formed are functional equivalents of halides. As such they are frequently employed as intermediates for reactions such as displacements, eliminations, reductions, and rearrangements. Selective mesylation of a vicinal diol is a common method of preparation of epoxides." Alkynyl mesylates can be used for the synthesis of trimethylsilyl allenes. Oxime mesylates undergo a Beckmann rearrangement upon treatment with a Lewis acid. Aromatic mesylates have been used as substrates for nucleophilic aromatic substitution. Mesylates are more reactive than tosylates toward nucleophilic substitution, but less reactive toward solvolysis. 

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