Nucleic Acids in Chemistry and Biology

a catalyst gave way to Lewis acid catalysts^19 (e.g.SnCl 4 or Hg(OAc) 2 ) and they, in turn, have been super-
seded by the use of silyl esters of strong acids, notably trimethylsilyl triflate,^20 trimethylsilyl nonaflate or
trimethylsilyl perchlorate. Some examples are shown in Figure 3.8. The silylated base is usually generated
immediately prior to the glycosylation by heating under reflux with a mixture of hexamethyldisilazane
(HMDS) and trimethylsilyl chloride (TMSCl).
Although, one-pot reactions have been described and are more convenient than handling moisture-sensitive
silylated bases, they generally result in lower overall yields of product. In earlier methods bis(trimethyl-
silyl)acetamide (BSA) was used, but the mixture of HMDS and TMSCl is generally preferred since the
by-product of the reaction (ammonium chloride) does not generally interfere with the subsequent glyco-
sylation reaction.

Nucleosides and Nucleotides 81

N

N N

N

N

TMS

RO O

RO O

O

O

O

R'

LA

RO O

RO O

O

R'

RO O

RO O

O

R'

RO O

RO OR

N

N

N

N

N

HO O

HO OH

N

N

N

N

NH 2

acyloxonium ion

TMS Bz

TMS N

N N

N

TMSNBz

TMS

TMS Bz

TMS

RO O

RO O

O

R'

N

N N

N

BzNTMS

TMS

RO O

RO OR

N

N

N

N

N

TMS

TMS

Bz

RO O

RO OR

N

N

N

N

N Bz

TMS

RO O

RO OR

N

N

N

N

N TMS

Bz

or

NH 4 OH

Figure 3.5 Rearrangement and formation of thermodynamic product N^9 -ribosylated purine (LAmercury salt
or Lewis acid e.g. TMSOTf)

AcO O

AcO OAc

N

N

N

N

Cl

Cl

HO O

HO OH

N

N

(ii) N

AcO O

AcO OAc

(i) OAc

Br

NO 2

Figure 3.6 The fusion method of nucleoside synthesis. Reagents: (i) 2,6-dichloropurine, acetic acid, melt at 150°C;
and (ii) 3-bromo-5-nitro-1,2,4-triazole, acetic acid, melt at 150°C