Dimethoxy trityl group

The introduction of methoxy substituents increases the ease of removal of trityl groups under acid conditions, but also decreases the selectivity for the primary hydroxyl group [377]. As a compromise, the monomethoxytrityl and dimethoxy-trityl groups found widespread use for the protection of primary positions of glycosides (see, e.g. Ref. [378]) and, especially for the OH-5 function of nucleosides [377]. The use of 6-nitroquinoline instead of pyridine was described [379] to improve the selectivity of monomethoxytritylation of nucleosides and nucleotides bearing free amino groups. A general and rapid procedure was developed for the preparation and isolation of 5 -0-dimethoxy trityl derivatives [380]. 

The dimethoxy trityl group at the 5-position in the derivative shown was removed preferentially by addition of the compound to a suspension of zinc bromide in nitromethane and work-up after 1 minute to afford a quantitative yield (ref. 186). 

In Schemes 8.204 and 8,205 above we showed that tritylamines can be generated by reductive amination and N-alkylation of trityiamine. However, N-alkyla-tion of amines by triphenylmethyl chloride (mp 110-112 °C) or triphenylmethyl bromide (mp 152-154 °C) in an aprotic solvent such as chloroform or chloro-form-DMF mixtures together with a base such as triethylamine is the most common method for introduting the trityl group [Scheme 8,212]434 4,4 -Dimethoxy-trityl tetrafluoroborate and 4i4, 4"-trimethoxytrityl tetrafluoroborate are also... 

Figure 8.3 Process of solid-phase phosphoramidite nucleotide synthesis. In the process, X = linker which is later incorporated into the polymer matrix DMTr = dimethoxy trityl protecting group which is removed by treatment with add to hberate the hydroxyl gronp for snbseqnent phosphitylation reaction. B s = protected purine and pyrimidine bases. Phosphite is oxidized with iodine in the presence of esterification agent to phosphotriester before the chain extension or it is oxidized at the completion of chain extension as shown...

Another protective group that has been used is dimethoxy trityl. The carbon 3 of deoxyribose has been protected with phosphoramide. Benzoyl groups are used to protect the adenine and guanine bases. Lately, in place of cross-linked polystyrene, controlled pore glass supports have become popular. 

Other spectroscopic procedures have been used to determine primary amino groups include those based on p-amino-benzaldehyde [128], ninhydrin [129], dimethoxy trityl chloride [129]. A spectrofluorimetric method has also been described [130]. 

The second step is removal of the DMT protecting group by treatment with dichloroacetic acid in CH2C12- The reaction occurs by an S14I mechanism and proceeds rapidly because of the stability of the tertiary, henzylic dimethoxy-trityl cation. 

A -Benzhydryl-substituted amino acids are considerably more stable than the Af-trityl derivatives (vide infra) to acidic reaction conditions nevertheless, they are deprotected by rather mild procedures. Several variations have been presented such as 4,4 -dimethoxy-benzhydryl (110), 4,4 -methoxy-2,2 -dimethylbenzhydryl (111), and 3,3, 4,4 -tetra-methoxybenzhydryl (112) derivatives (Scheme 53),b l but none of these protecting groups have found wider application. 

The strategy was chosen to (1) link the amino acid derivative to a polystyrene-supported hydroxylamine, (2) carry out the cyclization under Mitsunobu conditions, and (3) assemble a short peptide on the free amino group present in the ring. This approach has been shown to be suitable particularly for solid-phase synthesis, as the supported (3-lactam could be easily separated from the by-products of the Mitsunobu reaction. The linker employed was a polystyrene resin carrying 0-trityl-hydroxylamine linker, prepared according to the literature procedure [151]. After the deprotection of Fmoc group carried out with 20% piperidine in DMF, the L-cbz-serine (or L-cbz-threonine) was coupled using (4,6-Dimethoxy-[l, 3, 5]-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) [152] in M-methylpyrrolidone (NMP) in the presence of M,M-diisopropylethylamine (DIPEA) (Schemes 42 45). 

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