Z 1,6;3,4-dianhydro-2-azido-2-deoxy-β-d-galaktopyranosy (79) byly různými postupy připraveny 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluor-d-glukopyranosa (V), 2‑acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluor-d-glukopyranosa (VI) a 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluor-d-galaktopyranosa (VIII). Otevřením oxiranového kruhu látky 79 fluoridem byla připravena 1,6-anhydro-2-azido-2,4-dideoxy-4-fluor-β-d-glukopyranosa (90), která byla acetolýzou 1,6-anhydromůstku, redukcí azidu a acetylací převedena na 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluor-d-glukopyranosu (V). Při přípravě 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluor-d-glukopyranosy (VI) byl oxiranový kruh dianhydroderivátu 79 otevřen benzylalkoholem za vzniku 1,6-anhydr…o-2-azido-4-O-benzyl-2-deoxy-β-d-glukopyranosy (62), která reakcí s DAST poskytla 1,6-anhydro-2-azido-4-O-benzyl-2,3-dideoxy-3-fluor-β-d-glukopyranosu (63). Z fluorderivátu 63 byla 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluor-d-glukopyranosa (VI) připravena acetolýzou 1,6-anhydromůstku, hydrogenolýzou a acetylací. Příprava 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluor-d-galaktopyranosy (VIII) také využívala fluorderivát 63, který byl oxidativně debenzylován a Latrellovou-Daxovou inverzí konfigurace na C4 byla d-gluko konfigurace převedena na d‑galakto za vzniku 1,6-anhydro-2-azido-2,3-dideoxy-3-fluor-β-d-galaktopyranosy (82). Látka 82 poskytla 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluor-d-galaktopyranosu (VIII) otevřením 1,6-anhydromůstku, redukcí azidu a acetylací. Příprava 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluor-d-galaktopyranosy (VII) vycházela z 1,6;2,3-dianhydro-β-d-talopyranosy (64), která reakcí s DAST poskytla 1,6;2,3-dianhydro-4-deoxy-4-fluor-β-d-talopyranosu (65), ze které byl požadovaný produktVII připraven azidolýzou oxiranového kruhu, acetolýzou 1,6-anhydromůstku, redukcí azidu a acetylací.
ANNOTATION
2-Acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-d-glucopyranose (V), 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluoro-d-glucopyranose (VI) and 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluoro-d-galactopyranose (VIII) were prepared from 1,6;3,4-dianhydro-2-azido-2-deoxy-β-d-galactopyranose (79) by various methods. Oxirane ring-opening of dianhydroderivative 79 with fluoride gave 1,6-anhydro-2-azido-2,4-dideoxy-4-fluoro-β-d-glucopyranose (90), which was tranformed to 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-d-glucopyranose (V) by acetolysis of the internal acetal, reduction of azide and acetylation. The oxirane ring in dianhydroderivative 79 was opened by benzylalcohol yielding 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-β-d-glucopyr…anose (62), which subsequently reacted with DAST to give 1,6-anhydro-2-azido-4-O-benzyl-2,3-dideoxy-3-fluoro-β-d-glucopyranose (63). Cleavage of the internal acetal, hydrogenation and acetylation provided 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluoro-d-glucopyranose (VI). Fluoroderivative 63 in the synthesis of 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-3-fluoro-d-galactopyranose (VIII) was oxidatively debenzylated and following configural inversion at C4 provided 1,6-anhydro-2-azido-2,3-dideoxy-3-fluoro-β-d-galactopyranose (82). Compound 82 was transformed to VIII by acetolysis of the 1,6-anhydro bridge, reduction and acetylation. Preparation of 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-d-galactopyranose (VII) used 1,6;2,3-dianhydro-β-d-talopyranose (64) as a starting material. Compound 64 was fluorinated by DAST to give 1,6;2,3-dianhydro-4-deoxy-4-fluoro-β-d-talopyranose (65), which was transformed to 2‑acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-d-galactopyranose (VII) by azidolysis, cleavage of the 1,6-anhydro bridge, reduction and acetylation.
The printed version of the thesis is available at the department where the thesis was produced. Defence protocol and reviews are available at UCT Prague archive.
