150
2
General Synthetic Methods
⊡ Scheme 56
Application of TIPDS protecting group in the synthesis of a glyco(phospho)lipid
However, despite the attractive properties, which are inherent in the use of the TIPDS protecting group in sugar chemistry, its general applicability is limited, to some extension by the fact
that this group can not withstand acidic conditions, which are commonly used in carbohydrate
chemistry.
2.5.6 Di-tert -butylsilylene (DTBS) Group
The ditertbutylsilylenediyl is a convenient and versatile protecting group introduced by
Trost [340] and often used for the synthesis of anthracyclines [341] and nucleotide [342]
derivatives. The DTBS group is not as robust as isopropylidene or benzylidene acetals and
therefore its use is appropriate for systems requiring deprotection under very mild conditions.
DTBS derivatives survive hydroboration, mild oxidation, Lewis acids, mild protic acids, and
strong bases but hydrolysis occurs readily with HF in acetonitrile, HF·pyridine complex, or
TBAF.
The formation of the silylene derivatives is effected by treatment of the diol with ditertbutyldichlorosilane in the presence of 1-hydroxy-benzotriazole (HOBT) ( > Scheme 57) [340].
Ditertbutylsilyl ditriflate and 2,6-lutidine effects silylene formation faster and under milder
conditions than the less-reactive dichloride [343]. When the silylation is carried out in pyranoside derivatives, the reaction proceeds selectively at 1,3-diol groups of C-4 and C-6 positions
and the formation of the five-membered DTBS derivatives of 1,2 diols was not observed [344].
It has been shown that a DTBS group at the O4-O6 position of a galacto-type sugar directs
α-predominant selective glycosylation in spite of the presence of a participatory group at C-2
such as benzoyl or Troc groups [345] ( > Scheme 58). This new glycosylation method is a powerful strategy for the synthesis of α-galactosyl and galactosaminyl glycans [346,347].
2
General Synthetic Methods
⊡ Scheme 56
Application of TIPDS protecting group in the synthesis of a glyco(phospho)lipid
However, despite the attractive properties, which are inherent in the use of the TIPDS protecting group in sugar chemistry, its general applicability is limited, to some extension by the fact
that this group can not withstand acidic conditions, which are commonly used in carbohydrate
chemistry.
2.5.6 Di-tert -butylsilylene (DTBS) Group
The ditertbutylsilylenediyl is a convenient and versatile protecting group introduced by
Trost [340] and often used for the synthesis of anthracyclines [341] and nucleotide [342]
derivatives. The DTBS group is not as robust as isopropylidene or benzylidene acetals and
therefore its use is appropriate for systems requiring deprotection under very mild conditions.
DTBS derivatives survive hydroboration, mild oxidation, Lewis acids, mild protic acids, and
strong bases but hydrolysis occurs readily with HF in acetonitrile, HF·pyridine complex, or
TBAF.
The formation of the silylene derivatives is effected by treatment of the diol with ditertbutyldichlorosilane in the presence of 1-hydroxy-benzotriazole (HOBT) ( > Scheme 57) [340].
Ditertbutylsilyl ditriflate and 2,6-lutidine effects silylene formation faster and under milder
conditions than the less-reactive dichloride [343]. When the silylation is carried out in pyranoside derivatives, the reaction proceeds selectively at 1,3-diol groups of C-4 and C-6 positions
and the formation of the five-membered DTBS derivatives of 1,2 diols was not observed [344].
It has been shown that a DTBS group at the O4-O6 position of a galacto-type sugar directs
α-predominant selective glycosylation in spite of the presence of a participatory group at C-2
such as benzoyl or Troc groups [345] ( > Scheme 58). This new glycosylation method is a powerful strategy for the synthesis of α-galactosyl and galactosaminyl glycans [346,347].