C-nucleoside synthesis

We were first attracted to chiral pyrrolidines by the possibility of applying methods used in C-nucleoside synthesis (1) to the synthesis of the antiprotozoal antibiotic anisomycin (p from D-ribose (2). 

Friedel-Crafts coupling of an aromatic compound with an activated glycosyl donor is a classic, standard method for C-aryl glycoside synthesis [1,2]. Early interests were primarily centered at C-nucleoside synthesis, so that data were accumulated for the ribofuranosyl series with degradable aromatics to construct the nucleic base (Scheme 2) [5]. Equation (1)... 

Cox, P J, Simpkins, N S, An enantioselective deprotonation route to a versatile intermediate for C-nucleoside synthesis, Synlett, 321-323, 1991. 

In the presence of a Lewis acid such as SnCh, BF3 OEt2, ot TiC104, TMS-CN reacts with acetals to give cyanohydrin ethers. o-Ribofuranosyl cyanide, an important intermediate of C-nucleoside synthesis, is prepared from a furanosyl acetate (Scheme 23). ... 

Recently, C-nucleoside synthesis by glycosyl free radical coupling with protonated nitrogen heterocycles started to gain impetus. Thus, photoirradiation of the l-(2,5-anhydro-D-allonoyloxy)pyridine-2-thione derivative 798 gave the D-ribofuranosyl free radical 799 that couples with substituted pyridines to give a mixture of the two anomers of 2-pyridyl C-nucleosides... 

Microwave-assisted ring opening of epoxides with pyrimidine nudeobases provided rapid entry into C-nucleoside synthesis. The use of microwaves led to different selectivity from that resulting from conventional heating (Eq. 39b) [55b]. 

Photochemical decarboxylation in the presence of diacetoxyiodobenzenc and the appropriate heterocycle has been used to make some compounds related to C-nucleosides, such as 167.192 The preparation of a chloromethyl ketone related to 2,5-anhydro-D-allonic acid, and of potential use in C-nucleoside synthesis, is discussed in Chapter 3. 

A. P. Kozihowski and W. C. Floyd. Borohydride reduced cleavage of azo derivatives of j3-keto esters. A useful variant of the Japp-Klingemann reaction for C-nucleoside synthesis. Tetrahedron Letters, 1978,1, 19. 

Examples of synthesis of trifluoromethyl-substituted 1,2,4-triazines by transformation of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 49 ring are presented at Scheme 20. The anomeric C-glycosyl precursors 50, functionalized by an imidate group and appropriate for C-nucleoside synthesis were utilized as heterodienophiles in a Diels-Alder reaction with inverse electron demand to yield the 0-benzyl protected 5-( 3-D-ribofuranozyl)- and 5-(a-D-ribofuranosyl)-1,2,4-triazines 51 (Scheme 20) [30]. 

Maeba 1, Takeuchi T, lijima T, Furukawa H (1988) C-nucleosides. 7. Preparation and utility of 6-hydroxy-6-(2,3,5-tri-0-benzoyl-p-D-ribofuranosyl)-27/-pyran-3(67f)-one as a key intermediate of C-nucleoside synthesis. J Org Chem 53(7) 1401-1405. doi 10.1021/jo00242a012... 

---