Linkers sulfonyl

Since the discovery of SQ 83,360, compounds such as U-78,608 [123444-35-9] (64) having different linker groups between the hydroxypytidone group and the sulfonyl residue have been reported. U-78,608 and SQ 83,360 have similar in vitro and in vivo activity (45). 

Zhong HM, Greco MN, MaryanofF BE. Solid-phase synthesis of arginine-containing peptides by guanidine attachment to a sulfonyl linker. J Org Chem 1997 62 9326-9330. 

Syntheses of this class of compounds usually involve 1,2,5-thiadiazepine ring 333 (Figure 6) which is stable in the S-oxidized form and structurally represents cyclic pyrrole N-sulfonyl derivatives. Most of the synthetic strategies include formation of an S-Npyrroie bond in the early stages. A final cyclization step typically includes (i) intramolecular cyclization by creation of an N-X bond from a suitable pyrrole precursor or (ii) a 6 + 1 type cyclization that involves dielectrophilic species to form linker X and utilizes the nucleophilicity of the phenyl amino group and of the pyrrole ring at C2. Intramolecular processes with the formation... 

For some applications, it is useful to put a substrate on a solid support. Linkers that can be converted directly to desired functionality ( traceless ) are particularly valuable. Andrew M. Cammidge of the University of East Anglia and A. Ganesan of the University of Southampton independently (Chem. Commun. 2004, 1914, 1916) developed the polymeric sulfonyl chloride 9. The derived phenyl sulfonates are useful partners for transition-metal mediated cross coupling. 

Alternatively, sulfonamides can also be prepared by oxidation of sulfinamides with periodate (Entry 3, Table 8.8) or with MCPBA [125]. Polystyrene-bound sulfonyl chlorides, which can be prepared from polystyrene-bound sulfonic acids by treatment with PCI5, SOCI2 [126-129], CISO3H [130], or SO2CI2/PPI13 [131], react smoothly with amines to yield the corresponding sulfonamides (Entry 4, Table 8.8). Support-bound carbamates of primary aliphatic or aromatic amines can be N-sulfonylated in the presence of strong bases, and can therefore be used as backbone amide linkers for sulfonamides (Entries 5 and 6, Table 8.8). 

A survey of the literature reports regarding the synthesis of (3-lactam using carbohydrate precursors has recently been published by Furman et al. [215]. They have shown that the carbohydrates were used either as chiral tools or chiral auxiliaries. A few solid phase approaches have been outlined in the survey using the vinyl ether bound to the polymeric support through a sulfonyl linker. Two alternative modes of attachment of the vinyl ethers to the resin have been reported. 

Thus, gel-type polystyrene-sulfonyl-hydrazide resin 20, which originally was developed for carbonyl scavenging applications [30] can also serve as a linker for carbonyl compounds in solid phase synthesis and gives access to support-bound sulfonyl hydrazones 21 (Scheme 8)... 

In CHEC-II(1996) the detailed discussion of thiophenes as intermediates was, somewhat arbitrarily, limited to photochemical and electrocyclic processes. Additionally, reactions were included which destroy the aromatic thiophene skeleton to give rise to open chain molecules. In this scheme very recent applications of thiophenes such as thiophene-based amide linkers in solid-phase synthesis <2006JOC6734> or V-(2-thienyl)sulfonyl aldimins in chiral Mannich reactions <2006OL2977> did not be fit in. 

Villalgordo et al. [22, 23] as well as Gayo and Suto [25] developed a strategy to cleave pyrimidines from the solid support. After oxidation of the thioether-linkage 17, aromatic substitution of the sulfonyl unit was performed with different N-nucleophiles as amines and azides to give free amino- or azido-pyrimidines 19 (Scheme 16.5). To demonstrate the stability of the linker, the resin-bound derivatives were subjected to different reactions such as saponification, ester reduction, acid chloride formation or Mitsunobu alkylation. A similar approach was presented later on by Hwang and Gong in the SPOS of 2-aminobenzoxazoles [26]. 

A benzyl halide solid support If (Table 1) has been reported [77] that affords anchoring groups which are less labile than trityl anchors Ib-le but more labile than anchors to chloromethyl-PS (la). Resin If has been used to prepare amides and sulfonamides by reaction with an amine followed by acylation or sulfonylation, respectively, and cleavage using 95% TFA. When the same reaction sequence was conducted on an analogous resin Ig prepared from Tentagel AC (acid-cleavable linker), the products could be cleaved under milder conditions (5% TFA) because of the greater stability... 

The first reported solid-phase synthesis of head-to-tail cyclic peptides was based on the intramolecular aminolysis of resin-bound o-nitrophenyl esters. The cyclization proceeds concurrently to cleave the peptide from the resin, after deprotection and neutralization of the AT-terminal residue (Scheme 2A). Accordingly, Fridkin et al. [3] reported the preparation of several simple, unhindered cyclopeptides, such as cyc/o(Ala-Gly-Ala-Ala). Similarly, Flanigan and Marshall [4] obtained activation of the resin-bound peptide ester, after elongation of the peptide chain, by oxidation of the 4-(methyl-thio)phenyl (MTP) linker to a sulfonyl ester. Subsquent deblocking of the A-terminal residue and intramolecular condensation yielded the desired cyclic peptide. However, this method was found not to be suitable for the synthesis of longer and more hindered cyclic peptides [5]. 

Chiral vinyl ethers attached to a Wang resin through the p-oxyphenylsulfonyl linker, have been reported to give the [2+2] cycloaddition reaction with chloro-sulfonyl isocyanates (CSI) [226]. The intramolecular alkylation of the (3-lactam nitrogen atom gave mixtures of the corresponding diastereomeric clavams or oxacephams, (Scheme 102). 

Using a quite different approach, polymeric beads of supported ionic liquid palladium catalysts comprised of polymerized ionic liquid monomers and palladium complexes have been synthesized using traditional suspension polymerization methods [86]. Here, polymeric ionic liquid beads were made from polymerization of l-butyl-3-vinylimidazolium bis(trifluoromethyl sulfonyl)imide and poly(vinylalcohol) by heating with AlBN (2,2 -azobis(2-methylpropionitrile)) in the presence of l,l -bis[l,8-octyl)-3-vinylimidazolium bis(trifluoromethyl sulfonyl)imide as cross-linker (Scheme 5.6-6). The ionic liquid support beads proved to be thermally stable up 250 °C which is significantly higher than conventional vinyl resins. 

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