Biomedical Engineering Reference
In-Depth Information
1.
p
-TolSCl, AgOTf, -78°C
2.
1.
p
-TolSCl, AgOTf, -78°C
2.
O
BnO
OBn
STol
OBn
Ph
OBn
BnO
O
BnO
O
OBn
HO
STol
BnO
O
O
TrocHN
BnO
O
STol
OH
Ph
O
OBn
BnO
OBn
BnO
O
O
TrocHN
O
BnO
BnO
O
O
1.
p
-TolSCl, AgOTf, -78°C
O
2.
OBn
HO
OBn
O
OBn
OBn
O
BnO
OBn
OBn
O
O
O
OBn
O
O
OBn
O
N
3
O
BnO
BnO
O
N
3
BnO
OBn
α
(47%)
BnO
OBn
β
(23%)
SCHEME 12.19
Thioglycoside preactivation with a sulfenyl triflate.
axial glycosides [65] and even to 1,2-
trans
-axial glycosides [66]. A variation on the
theme results in the formation of 2-deoxy-2-sulfonamido-
-glycosides as required for
the formation of the initial disaccharide in Scheme 12.10 [67]. Application of this
chemistry to the synthesis of Globo-H resulted in the synthesis of 2
b
-(1
!
3)- and
b
b
-(1
!
4)-galactans with full control of stereochemistry [68].
12.3.4. Preactivation of Thioglycosides
Alternatively, avoiding the need for reactivity differentiated donors altogether, and
generalizing the work of Kahne [17a,69] and van Boom [70] with sulfoxide donors,
Huang developed a low-temperature thioglycoside preactivation protocol with sul-
fenyl triflates prior to the addition of a hydroxyl thioglycoside [71] (Scheme 12.19).
The stability and commercial availability of 4-nitrobenzenesulfenyl chloride should
increase the applicability of this method [72], which may also be conducted with the
combination of 1-benzenesulfinyl piperidine and triflic anhydride as the activating
cocktail [73]. This method enabled Huang and coworkers to achieve a one-pot syn-
thesis of Globo-H with 47% yield in only five steps and with satisfactory selectivity
for each glycosylation [74].
12.3.5. Programmable Reactivity-Based One-Pot Strategy
The Globo-H hexasaccharide also serves to illustrate the “programmable reactivity-
based one-pot strategy” approach to the synthesis of oligosaccharides. Ley and
coworkers [75] and Wong and coworkers [76] have developed reactivity scales for
thioglycoside donors that enable strategies to be planned, in which one thioglycoside
donor is activated selectively in the presence of a hydroxyl thioglycoside [76].
After the coupling reaction (Scheme 12.20), a second less reactive hydroxyl thio-
glycosidemay be added and a second coupling conducted, albeit with harsher reaction
conditions and longer reaction times. The relative reactivities of the acceptors are
tuned by the use of different electron-donating (benzyl ether and 2,2,2-trichlor-
oethylcarbamate) or electron-withdrawing groups (benzoyl,
p-
nitrobenzoyl, and
o-
chlorobenzyl ethers) and their reactivity can be quantitatively evaluated [75,76]
(Wong's relative reactivities toward peracetyl
tolylthiomannoside are given in
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