4,4 -Dimethoxy-3"- trityl

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]. 

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... 

Simple alkyl phosphonate diesters bearing a 2-pyridyl moiety are known to display a wide range of biological activities as well as having numerous technological applications. This functionality has now been incorporated in phosphonate nucleotide dimers (94). The bis([4,4 -dimethoxy]trityl)-dithymidine //-phos-phonates afforded (94) quantitatively upon treatment with N-methoxypyridinium tosylate in the presence of DBU. The reaction was rapid and proceeded stereospecifically. ... 

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). 

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. 

Dimethoxy-3 - [A-(imidazolylethyl)carbamoyl]trityl Ether (lETr-OR) ... 

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

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. 

Because of the availability of many required precursors, a useful method that is free from the steric demands of the trityl procedure is to react derivatives of (MeO-cyclohexadiene) Fe(CO)3 or cognate complexes with acids under vigorous conditions to cause proton-induced rearrangement of the initial complex structure, with loss of OMe e.g., in the 1,3-dimethoxy complex X which by route b yields the synthetically important XF . The alternative route a occurs to about 10% with sulfuric acid, but not with TFA. The mechanisms have been confirmed with deuterated acid . With optically active complexes some racemization may occur . 

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). 

Phenalenium ring. Trityl perchlorate added to a soln. of l-[a-(3,4-dimethoxy-phenyl)-a-morpholino]benzyl-2-methoxynaphthalene in glacial acetic acid containing 70%-HC104, stirred and heated 1.5 hrs. at 80-90° 6,9,10-trimethoxy-... 

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