4-tert-Butyldimethylsilyl

Fig. 4. Synthesis of monensin from homochiial natural products TBS = tert-butyldimethylsilyl chloride.

Recently, multidimensional GC has been employed in enantioselective analysis by placing a chiral stationary phase such as a cyclodextrin in the second column. Typically, switching valves are used to heart-cut the appropriate portion of the separation from a non-chiral column into a chiral column. Heil et al. used a dual column system consisting of a non-chiral pre-column (30 m X 0.25 mm X 0.38 p.m, PS-268) and a chiral (30 m X 0.32 mm X 0.64 p.m, heptakis(2,3-di-(9-methyl-6-(9-tert-butyldimethylsilyl)-(3-cyclodextrin) (TBDM-CD) analytical column to separate derivatized urinary organic acids that are indicative of metabolic diseases such as short bowel syndrome, phenylketonuria, tyrosinaemia, and others. They used a FID following the pre-column and an ion trap mass-selective detector following the... 

Ketone 13 possesses the requisite structural features for an a-chelation-controlled carbonyl addition reaction.9-11 Treatment of 13 with 3-methyl-3-butenylmagnesium bromide leads, through the intermediacy of a five-membered chelate, to the formation of intermediate 12 together with a small amount of the C-12 epimer. The degree of stereoselectivity (ca. 50 1 in favor of the desired compound 12) exhibited in this substrate-stereocontrolled addition reaction is exceptional. It is instructive to note that sequential treatment of lactone 14 with 3-methyl-3-butenylmagnesium bromide and tert-butyldimethylsilyl chloride, followed by exposure of the resultant ketone to methylmagnesium bromide, produces the C-12 epimer of intermediate 12 with the same 50 1 stereoselectivity. 

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

Diazoester aziridinations may be carried out in ionic liquids [39]. Other carbene equivalents have been investigated in aziridination reactions, though not to the same extent as diazocarbonyl compounds. Dibromo(tert-butyldimethylsilyl)me-thyllithium, for example, aziridinates N-arylimines to give l-bromo-2-aryl-3-silyla-ziridines these compounds function as useful synthetic intermediates, reacting... 

N-Oxides 986 are transformed by tert-butyldimethylsilyl triflate 987 into the reactive intermediates 988, which rearrange in the presence of methyllithium in THF, followed by PhMgBr in toluene via 989, to 990 ]77, 77 a]. Subsequent work demonstrated that the intermediates 989 react with Me3SiCN 18 in the presence of TiCl to give the a-cyanoamines 991 ]78]. Likewise, the N-oxide 992 affords, with 18 in the presence of 986, the a-cyanoamine 993 in 63% yield. The N-oxide 994 is, furthermore, converted by MesSiCN 18 in 61% yield into the a-cyanoamine 995, whereas the N-oxide of tribenzylamine 996 is converted by 18, 78% yield, into the a-cyanoamine 997 [78, 79] (Scheme 7.24). 

Treatment of the sulfoxide 1222 a with tert-butyldimethylsilyl chloride 85 a and excess imidazole in DMF at 25 °C furnishes the imidazole derivative 1223a in 70% yield, whereas the phenyl derivative 1222b affords, besides 47% of 1223b , the cyclized product 1224 in 24% yield and 94 a and imidazole hydrochloride [34] (Scheme 8.14). Reaction of 1225 with N-(trimethylsilyl)imidazole 1219 at 170°C affords 1226 in 50% yield [35]. 

The tert-butyldimethylsilyl (TBDMS) protection of 50 gave a silyl ether... 

Synthesis of geranyl 6-0-fl-o-xylopyranosyl-(3-D-glucopyranoside (82) Tert-butyldimethylsilylation of 51 gave a silyl ether (84, 63% yield), which was subjected to benzoylation to give a benzoate (85) in 71% yield. Desilylation of 85... 

Purdon JG, Pagotto JG, Miller RK. 1989. Preparation, stability, and quantitative analysis by gas chromatography and gas chromatography-electron impact mass spectrometry of tert-butyldimethylsilyl derivatives of some alkylphosphonic and alkyl methylphosphonic acids. J Chromatogr 475 261-272. 

The HEPT and TIBO derivatives were discovered as the result of a systematic evaluation for anti-HIV activity in cell culture. They were later found to achieve their anti-HIV-1 activity through an interaction with the HIV-1 RT. In contrast, nevirapine, pyridinone, and BHAP emerged from a screening program for HIV-1 RT inhibitors. The anti-HIV-1 activity of these compounds was subsequently confirmed in cell culture. Like the HEPT and TIBO derivatives, the 2, 5 -bis-0-(tert-butyldimethylsilyl)-3 -spiro-5" -(4" -amino-1", 2" -oxathiole-2", 2" -dioxide)-pyrimidine (TS AO) derivatives (Fig. 9) [65,66] and a-anilinophenylacetamides (a-APA) (Fig. 10) [67] were discovered through the evaluation of their anti-HIV activity in cell culture. Subsequently, they were found to act as specific inhibitors of HIV-1 RT. 

Balzarini J, Perez-Perez M-J, San-Felix A, Schols D, Perno C-F, Vandamme A-M, Camarasa M-J, De Clercq E. 2, 5 -Bis-0-(tert-Butyldimethylsilyl)-3 -spiro- 5" -(4" -amino-1", 2" -oxathiole-2", 2" -dioxide)pyrimidine (TSAO) nucleoside analogues highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase. Proc Natl Acad Sci USA 1992 89 4392-4396. 

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