Tetra synthesis protocols

Two additional developments that impacted the elaboration of synthesis protocols of proanthocyanidins via catechin (2) and epicatechin (3) derivatives and/or analogues, involved the transformation of readily available and inexpensive catechin (2) into the considerably more expensive epicatechin (3), and the design of experimental conditions permitting 0-benzylation of the phenolic hydroxy groups of flavan-3-ols in high yield. The transformation of catechin (2) into tetra-0-benzylepicatechin (52) (Scheme 7) involved the per-0-benzylation of the phenolic hydroxy groups of catechin (2) to afford tetra-0-benzylcatechin (50) in approximately 20% yield. Inversion of the configuration at C-3 was accomplished by oxidation to the... 

The synthetic protocol (Scheme 11.2) toward the flavan-3-ol permethylaryl ethers is based upon the transformation of rc7ro-chalcones into 1,3-diarylpropenes. These compounds are then subjected to asymmetric dihydroxylation to give diarylpropan-l,2-diols that are used as chirons for essentially enantiopure flavan-3-ols. The protocol is demonstrated in Scheme 11.2 for the synthesis of the tetra-(9-methyl-3-(9-acetyl derivatives 61a, 61b, 62a, and 62b of (-l-)-catechin (2), (—)-e 7-catechin, (—)-epicatechin (3), and (+)-e 7-epicatechin (4). ... 

On the other hand, the addition of a quaternary ammonium salt to the reaction medium accelerates the isomerization of the radical intermediate [36]. Thus, the epoxidation of c/j-stilbene in the presence of A -benzylquinine salt gives rranr-stilbene oxide with 90% ee as major product (Table 6B.1, entry 24). This protocol provides an effective method for the synthesis of trans-epoxides. In contrast to the epoxidation of c/s-di- and tri-substituted olefins for which complexes 11-13 are the catalysts of choice, the best catalyst for the epoxidation of tetra-substituted conjugated olefins varies with substrates (Table 6B.1, entries 27 and 28) [37]. The asymmetric epoxidation of 6-bromo-2,2,3,4-tetramethylchromene is well-promoted by complex 14 and that of 2-methyl-3-phenylindene, by complex 12a. 

In another application of catalytic glycosylation with triflic acid, two disaccharides were synthesized with donors bearing trichloroacetimidate function and then the disaccharides thus prepared were condensed in a similar manner to a tetrasaccharide757 (1,2-dichloroethane, 55°C, 1.5 h, 50-85% yields). The same protocol was used in the synthesis of a decasaccharide from mono-, tetra-, and pentasaccharide building blocks.758 The trichloroacetimidate procedure has been successfully used in the glycosylation of /3-cyclodextrins promoted by triflic acid.759 760... 

The synthesis of nucleoside diphosphates is best achieved using the Poulter reaction,9 which involves reaction of the tris(tetra-n-butylammonium) salt of pyrophosphate with a nucleoside 5 -tosylate in acetonitrile. A general procedure for the synthesis of nucleoside tosylates of thymidine and 2 -deoxyadenosine is included (Protocol 15), whilst the syntheses of the other tosylates (including ribonucleosides) have been described using related procedures. Simple modification of the protocol, whereby the tetra-n-butylammonium salt of pyrophosphoric acid is replaced by methylene or difluomethylene bis phosphonate, allows the synthesis of hydrolytically stable dNTP analogues.10... 

Derivative 13 was deprotected to give the triheptoside backbone of the Salmonella core [19], but the protecting pattern in 13 was also chosen to allow further synthesis of core structures. Thus, debenzylation of 13 to give the 2, 3, 4 -triol, followed by the orthoester protocol, once more gave a 3 -OH acceptor (14), which was reacted with methyl 2,3,4,6-tetra-O-benzyl-l-thio- -o-gluco-pyranoside and DMTST to give the tetrasaccharide 15 (Scheme 7). 

An efficient and highly enantio- and diastereoselective bromocycliza-tion-desymmetrization of olefmic 1,3-diols used a cyclic sulfide as catalyst. Olefmic 1,3-diols as substrates gave substituted THFs with up to three ste-reogenic centers, with two tetra-substituted carbons. This protocol represents the first case of a monofunctional C2-symmetric Lewis basic sulfide-catalyzed enantioselective bromoetherification reaction, which was applicable to the synthesis of a key intermediate to the orally active antifungal drug posaconazole (Noxafil) (14JA5627). 

The Au(I)-catalyzed version of Gabriele s protocol for the synthesis of pyrroles was recently reported by Gagosz et td. (Scheme 8.82) [271]. It was demonstrated that N-tosyl-protected (Z)-(2-en-4-ynyl)amines 219 could undergo a facUe cydoisomeriza-tion into pyrroles 220 in the presence of cationic bis(trifluoromethanesulfonyl) imidate Au(I) complexes, very robust catalysts. Notably, tri- and tetra-substituted pyrroles 220 were synthesized in excellent yields and under very mild conditions within 5 min reaction time. 

A number of 4-1-1 protocols for the synthesis of pyrrole cores featuring the Cu (I)primary amine derivatives as the key carbon-heteroatom bond forming reaction have been reported recently. Thus, Buchwald described an efficient Cu(I)-catalyzed synthesis of tri-, tetra-, and penta-substituted pyrroles 302 from 1,4-dihalo-l,3-dienes 300 and carbamates 281 (Scheme 8.107) [305]. This methodology displayed excellent functional group compatibility, providing good to... 

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