Organic Chemistry of Drug Synthesis. Volume 7

HO O

O

THP O

O

THPO

68 69

THP = tetrahydropyrranyl

Selectride

OH

70

CH 3 C 6 H 4 SO 2 Cl

N

N NH

N

NH 2

N

N

N

NH 2

THPO

N

OTHP

71

72

73

H 3 O+ N C^6 H^5 COCl

N

N

NHCOC 6 H 5

OTHP

N

N

N

NHCOC 6 H 5

OH

74

P

O

CH 3 C 6 H 5 SO (^3) OOiiPrPr
P
O
OOiPriPr
NaH
N
N
N
NHCOC 6 H 5
O
O 3 SC 6 H 4 CH 3
THPO
P
O
OOHH
N
N
N
NH 2
O
75
77 78
76
NN
N N
Replacement of one of the carbon atoms in the sugar moiety by oxygen,
in effect converting that ring to an acetal, leads to yet another false sub-
strate for viral reverse transcriptase. Glycosilation of the silylated purine
( 79 ) with chiral dioxolane ( 80 ), prepared in several steps from anhydro-
mannose, in the presence of ammonium nitrate affords the coupling
product as a mixture of anomers. The mixture of products is then separated
on a chromatographic column. The desired diastereomer ( 81 ) is the reacted
N
N N
N
Cl
F
Si(CH 3 ) 3

• O
  tBuPh 3 SiO O OCOCH 3
  79
  80
  N
  N N
  N
  Cl
  F
  O
  tBuPh 3 SiO O
  tBuPh 3 SiO
  81
  NH 3
  N
  N N
  N
  NH 2
  H 2 N
  O
  O
  83
  Bu 4 F
  N
  N N
  N
  Cl
  NH 2
  O
  tBuPh 3 SiO O
  82
  N
  N N
  N
  NH 2
  H 2 N
  O
  HO O
  84
  NH 3
  198 BICYCLIC FUSED HETEROCYCLES