Methyl groups protective function

Besides its protective function of the labile phosphine group, the BHj group activates the adjacent substituents such as methyl group or P-H bond to deprotonation with a strong base [78]. This methodology provides an efficient alternative to the difficult synthesis of a variety of optically active tertiary phosphine derivatives, as will be described in Sect. 3. 

The next series of four preparations describe the synthesis and/or use of recently introduced reagents for functional group protection. The first in this series describes the preparation of 2-TRIMETHYLSILYLETHANE-SULFONYL CHLORIDE (SEC-C1), an effective reagent for protection of primary and secondary amines as the corresponding sulfonamide. The SES-protected amines are stable intermediates which can be readily purified treatment with CsF in DMF or TBAF in acetonitrile liberates the parent amine. The preparation of (l/S,2,S)-METHYL-30,40-(l, 2 -DIMETHOX YCYCLOHEXANE -l, 2 - DIYL) - a -d -M ANNOPYRANO-... 

In the thiol 79 and the sulfinic acid 80, two new acidic functionalities are now present in the 2 -position of a m-terphenyl system and should be incorporable into concave structures by a double bridging of the m-terphenyl. For the acetyl-protected thiol 78, the corresponding concave thiol acetate 42 (Scheme 7) could be obtained after tetrabromination of the four methyl groups and bridging with m-phenylenedithiol (see Sect. 2.3). 

The structure of alpha-0 is designed to overcome these two restrictions. A methyl group on the oxygen (the O-methyl) removes the polarity restriction. A methyl group next to the amine function (the alpha-methyl) protects the molecule from enzymatic attack. With the two obstacles removed, this compound apparently has easy access directly to the brain. Hence, alpha,O-dimethylserotonin (a,0-DMS) goes directly into the central nervous system and has proved to be one of the most potent tryptamines yet described. And it is active following oral administration, where it is exposed to all of the body s protective machinery. 

Reaction with LiAlH4 at -78 °C selectively reduces the keto-function from the face opposite to the angular methyl group. Subsequently, the resulting alcohol is protected as TMS ether 58. 

Immediately after transcription, the 5 phosphate is removed, guanosyl transferase adds a G residue linked via a 5 -5 covalent bond, and this is methylated to form a 7-methylguanosine (m7G) cap (methylated in N-7 position of the base). The ribose residues of either the adjacent one or two nucleotides may also be methylated by methyl group addition to the 2 OH of the sugar. The cap protects the 5 end of the mRNA against ribonuclease degradation and also functions in the initiation of protein synthesis. 

Reduction of the olefinic bond in 12 and Swem oxidation of the free carbinol function provided ketone 53, onto which installation of the methyl group was performed by reaction with methylmagnesium chloride in THF. After protection of the resulting tertiary alcohol as a TBS-ether, fully protected triol 54 was obtained with a useful 80% diastereomeric excess. Acetonide deblocking and oxidative fission of the diol formed led to aldehyde 55, ready for the planned cyclization step. Exposure of aldehyde 55 to TBSOTTDIPEA reagent system smoothly resulted in formation of the desired bicyclic adducts 56 and 57 which were isolated in a 82% combined yield (60 40 ratio). 

Further reactions are provided by the mild oxidation of the methyl groups in 2,8-dimethylphenoxazine (protected by -acetylation) which yields V-acetylphenoxazine-2,8-dicarboxylic acid (44, X = OH), from which various functional derivatives have been prepared (44, X = C1,NH2, OR,NR2).6181... 

During a synthesis of quinone imine precursors to the Dynemicins, Myers and co-workers100 encountered problems with the lability of the dimethyl acetal function in 56,1 [Scheme 1.56] whilst removing the robust phenolic methyl group using sodium ethanethiolate in hot DMF, However prior conversion of the free hydroxy function in the substrate to the magnesium salt 56.2 by reaction with ethylmagnesium bromide afforded protection for the dimethylacetal under the strenuous conditions of nucleophilic demethylation. 

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