Linker silyl ether

Silyl-derived linker 36 was prepared in three steps from a silyl ether of serine and incorporated for Fmoc/tBu-based assembly of protected gly-copeptide blocks (Scheme 11) [42]. The a-carboxylic acid function of serine was protected as an allyl ester. Deprotection by a Pd(0) catalyst in the presence of dimedone liberated the carboxylic acid in order for subsequent... 

Nakamura K, Hanai N, Kanno M, Kobayashi A, Ohnishi Y, Ito Y, Nakahara Y. Design and synthesis of silyl ether-based linker for solid-phase synthesis of glycopeptides. Tetrahedron Lett 1999 40 515-518. 

Boehm TL, Showalter HDH. Development of a novel silyl ether linker for solid-phase organic synthesis. J Org Chem 1996 61 6498-6499. 

The galactosyl glycal 72 was bound to solid phase via a silyl ether linker. Epoxidation of the glycal using 2,2-dimethyldioxirane and subsequent electrophilic activation of the epoxide resulted in the glycosylation of 3,4-di-O-benzyl glucal 73. After acetylation of the product, the polymer-linked trisaccharide 74 was obtained. 

A class of photolabile linkers has been developed to circumvent the use of silyl ethers as linkers and allow for the use of temporary silyl protecting groups.34,35 Photolabile linkers, such as 2, often involve the use of o-nitrobenzyl ether groups. This functional group is stable to a variety of conditions however, cleavage from the polymer support is often slow and... 

Silyl ether Alcohols Silyl-type linkers [16, 17]... 

The linker was prepared starting from serine benzyl ester 68 according to Scheme 30. First, the hydroxyl function was protected as a silyl ether. The amino group was then reacted with phosgene to allow for further reaction with a substituted phenol (the educt). Finally, the benzyl ester was subjected to hydrogenolysis yielding unit 69, with the latter bearing a carboxylic acid function for attachment to the solid support to yield 66 ready for use in combinatorial synthesis. 

Two diastereoisomeric allylic silyl ethers 133 and 134 were first investigated and in both cases, the desired radical cyclization products were not observed. In the case of 133, cyclization proceeded exclusively in a 6-endo mode, affording diol 135 after oxidative cleavage of the silyl linker. The preference for 6-ring formation was attributed to the conformational rigidity of the allylic system and the less hindered nature of the distal sp -... 

The use of silyl ethers as protecting groups for the hydroxyl functionality is well known, and their adaption into linker units was a welcome addition to the SPOS literature. Thus, many silyl linker units have been reported for alcohols, and a selection is illustrated in Table 1.15. Owing to the large number of reported examples, a complete discussion of each is beyond the scope of this chapter, but Spivey has written a complete review. Much like deprotection of their solution-phase counterparts, cleavage from silyl linkers can be achieved using, for example, HE (Table 1.15, Entries 1-3 and 6) , TBAF (Table 1.15, Entries AcOH (Table 1.15, Entries 1 and 4) °, or TEA (Table 1.15,Entry 5). Beyond alcohols, other traditional sUyl linker units are useful for SPOS with other substrates such as amines (Table 1.15, Entry... 

Development of Diisopropylsilyl Solid Supports. A diiso-propylsilyl linker-based sohd support (62) can be synthesized in six steps beginning with silylation of 4-lithioanisole (60) with chlorodiisopropylsilane to form silane (61, eq 19). Substrate loading can be accompUshed by activation of the silane to the silyl triflate followed by addition of the substrate alcohol to form the silyl ether-linked substrate (61). Once the small molecule synthesized on the bead is ready for cleavage, treatment with a 5% solution of HF/pyridine in THF accomplishes efficient recovery of the desired small molecule and in high purity. ... 

Boel996 Boehm, T.L. and Showalter, H.D.H., Development of a Novel Silyl Ether Linker for Solid-Phase Organic Synthesis, J. Org. Chem., 61 (1996) 6498-6499. 

Silyl linkers are very common in solid phase chemistry in their function as alcohol-protecting groups [332-338]. Cleavage from those silyl ether resins... 

Details of the Janda-Chen synthesis were as follows. A tetrahydropyran (THP) linker was attached to the NCPS support enabling attachment of alcohols via THP ether formation.13 The THP-NCPS resin 1 is derivatized with / -(+)-4-hydroxy-2-cyclopentanone 2, giving the THP ether-based resin 3, followed by coupling of the C13 20 fragment by enone-cuprate addition. The cuprate required was generated from the corresponding E-vinyl stannane 4. The resulting enolate was trapped as the silyl end ether... 

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