O-Glycosyl Donors
3.4
643
5.6.4 Total Synthesis of Agelagalastatin
The total synthesis of agelagalastatin, an antineoplastic glycosphingolipid, has been described
by Kim and co-workers [217]. The retrosynthesis, outlined in > Scheme 72, involved a β-Dgalactofuranosylation, an α-D-galactofuranosylation, and a final α-D-galactopyranosylation.
The β-D-galactofuranosylation was achieved in 79% yield via neighboring group participation of the pivaloyl group at O2 in compound 445. The α-D-galactofuranosylation to 441,
took place with 91% yield with a nonparticipant benzyl group at O2 in donor 443. The final
α-D-galactopyranosylation ( > Scheme 73) was carried out with CB trisaccharide donor 441
furnishing compound 447 in 77% yield as a 1.4:1 (α/β) mixture of saccharides. The efficiency of this coupling was improved by conversion of the CB trisaccharide donor to glycosyl
fluoride 448. Treatment of 441 with TF 2 O/DTBMP followed by HF-pyridine, as a source of
fluoride, yielded glycosyl fluoride 448. The glycosylation of acceptor 442 with glycosyl fluoride 448, then gave the target protected agelagalastatin 447, in 72% yield as the pure α-isomer.
5.7 Conversion of 2 -Carboxybenzyl Glycosides
into Other Glycosyl Donors
CB glycosides have been converted to phenyl 1-thio glycosides and glycosyl fluorides in onepot operations [218]. Thus, treatment of CB glycosyl donors with TF 2 O/DTBMP in CH 2 Cl 2
at −78 °C for 10 min followed by addition of PhSH furnished thioglycosides, e. g. 451, 453
( > Scheme 74), whereas treatment with DAST or HF-pyridine (see > Scheme 73) yielded
the corresponding glycosyl fluorides, e. g. 449, 452 ( > Scheme 74). The high β-selectivity
observed in the formation of glycosyl fluoride 452 and thioglycoside 453 from 4,6-O-benzylidenemannopyranoside 396 was ascribed to the presence of a highly reactive 4,6-O-benzylidenemannopyranosyl α-triflate, in keeping with previously mentioned findings.
⊡ Scheme 74
Conversion of CB glycosides to glycosyl fluorides and thiophenyl glycosides
3.4
643
5.6.4 Total Synthesis of Agelagalastatin
The total synthesis of agelagalastatin, an antineoplastic glycosphingolipid, has been described
by Kim and co-workers [217]. The retrosynthesis, outlined in > Scheme 72, involved a β-Dgalactofuranosylation, an α-D-galactofuranosylation, and a final α-D-galactopyranosylation.
The β-D-galactofuranosylation was achieved in 79% yield via neighboring group participation of the pivaloyl group at O2 in compound 445. The α-D-galactofuranosylation to 441,
took place with 91% yield with a nonparticipant benzyl group at O2 in donor 443. The final
α-D-galactopyranosylation ( > Scheme 73) was carried out with CB trisaccharide donor 441
furnishing compound 447 in 77% yield as a 1.4:1 (α/β) mixture of saccharides. The efficiency of this coupling was improved by conversion of the CB trisaccharide donor to glycosyl
fluoride 448. Treatment of 441 with TF 2 O/DTBMP followed by HF-pyridine, as a source of
fluoride, yielded glycosyl fluoride 448. The glycosylation of acceptor 442 with glycosyl fluoride 448, then gave the target protected agelagalastatin 447, in 72% yield as the pure α-isomer.
5.7 Conversion of 2 -Carboxybenzyl Glycosides
into Other Glycosyl Donors
CB glycosides have been converted to phenyl 1-thio glycosides and glycosyl fluorides in onepot operations [218]. Thus, treatment of CB glycosyl donors with TF 2 O/DTBMP in CH 2 Cl 2
at −78 °C for 10 min followed by addition of PhSH furnished thioglycosides, e. g. 451, 453
( > Scheme 74), whereas treatment with DAST or HF-pyridine (see > Scheme 73) yielded
the corresponding glycosyl fluorides, e. g. 449, 452 ( > Scheme 74). The high β-selectivity
observed in the formation of glycosyl fluoride 452 and thioglycoside 453 from 4,6-O-benzylidenemannopyranoside 396 was ascribed to the presence of a highly reactive 4,6-O-benzylidenemannopyranosyl α-triflate, in keeping with previously mentioned findings.
⊡ Scheme 74
Conversion of CB glycosides to glycosyl fluorides and thiophenyl glycosides