糖化学保护基3

Regioselectivity of reductive ring opening
Ph Me3N.BH3/AlCl3 toluene 52% OH BnO BnO O OBn O BnO O O OBn
OMe
Me3N.BH3/AlCl3 OMe THF 72% OBn O HO BnO OBn OMe
作业
Ph
OH OH O BnO OBn OMe OMe OMe DMF/CSA A
O O O BnO OBn OMe AlCl3/LiAlH 4 Et2 O-CH 2Cl2 B
Ph O O O BnO OBn OMe NaBH3 CN Et2 O/HCl C
O O O BnO OBn OMe TFA/CH 2Cl2 D
Benzylidene acetals
Ph
• 4,6-O-Acetals
O 1,3-cis
十氢萘的构型
O O
• Six-membered rings
RO
OR RO O OR RO
• Selective protection 1,3-cis/trans diols and 1,2-cis diols
Ph OO O RO OR Benzylidene OMe SEt MeO O O HO O OH SEt O Cyclo-hexane-1,2 -diacetal (CDA) O O Me O OH O Me O OH i-Propylidene OMe O
O OH OMe Dispiroketal (Dispoke)
Classification
• Benzylidene acetals • Isopropylidene acetals • Dispirodiketal(Dispoke) and cyclohexane1,2-diacetal(CDA) groups • Other acetals
Characteristics
Isopropylidene acetals
• Protection of 1,2-cisdiols and 1,3-diols • Five-membered 1,3dioxoane are preferred over sixmembered rings • 1,2-isopropylidene are more stable than other isopropylidenes
Kinetic product
HO
Me O OH
Protection(4)
Me
OH HO HO O OH OH
O O O OH O O Me Me
Acetone Me H2SO4 56%
Me Me
O O O OR O O Me Me
HO HO AcOH/H2O O OR O Me O Me
83%
Exocyclic isopropylidene acetals Endocyclic isopropylidene acetals
• Acid-catalytic alcoholysis
Ph OO O RO OR OMe
80% HOAc, TFA/DCM/H2O, CSA/MeOH
HO CSA/MeOH 91% RO
OH O OR OMe
Regioselectivity of reductive ring opening
Ph OO O BnO OBn Ph OO O BnO OBn OMe NaCNBH3 HCl/Et2O 93% OH OBn O BnO OBn OMe AlCl3/LiAlH4 Et2O-CH2Cl2 OMe 89% BnO BnO OBn OH O OMe
作业
OH HO HO O OH OH Ac2 O (12 eqiv) NaOAc A HO HO OH O OH NH 2 OH O PivCl / Py OH OMe OAc AcO AcO O OAc OAc (NH4 )2 CO 3 DMF E C HO HO O 1) phthalic anhydride NH2 OMe 2) Ac2 O D Ac 2O (12 eqiv) NaOAc B
Ph
O O RO
1,3-trans
Benzylidene acetals
• Protection • Deprotection • Regioselectivity of reductive ring opening
Protection(1)
• Original
Ph HO OH O RO OR OMe OO CHO ZnCl2 RO OR OMe O
OH HO HO
OBn BnO O O NaN 3 / DMF OMe
BnO BnO
N3 O
BnO 1) Pd / H 2 2) Ac2 O / Py OMe OAc BnO
N
Protecting Groups
Acetal and ketal Protecting Groups 缩醛和缩酮保护基
O O
R' R3
R'=H, alkyl
R2 O O R' R3
改良方法： R2
R1
OH OH
MeO + MeO
R' R3
酸催化 (除水) R1
R'=H, alkyl R2 OH OH + OMe 酸催化 (除水) R1 O O
R2 R1
Characteristics
• Dihydroxy protecting 双羟基的保护 • Rings (Usually five or six-membered)环的大 小 • Selective formation and cleavage 选择性 • Stability 稳定性
多羟基化合物的缩醛和缩酮保护
环的大小，稳定性
缩醛（酮）的化学性质
糖环中二醇的位置和空间构型：
1,2- diol, 1,3-diol Cis- / Trans- 形成和断裂的选择性
缩醛（酮）的形成方法：
R2
经典方法：
R1
OH OH
R' + O R3
酸催化 大比率投料 除水(除水剂,移除)
R2 R1
Protection(2)
Me Me HO OH O OH OMe HO OH O HO OH OMe OMe CSA/DMF 61% OO O HO 1,3-diols Me2C(OMe)2 CSA 93% OH OMe O Me O OH 1,2-cis-diols OMe Thermodynamic product
Me Me OO O HO 1,3-diols Me O OH O Me O O O Me 1,2-cis-diols Me OH OH
Protection(1)
• Original Dry acetone in the presence of an acid catalyst (PPT) • Process CuSO4 as a dehydrating agent to trap water • Recently 2,2-dimethoxypropane and 2-methoxypropene with catalytic amount acid
Deprotection(1)
• Mild aqueous acid hydrolysis (AcOH/H2O) • Catalytic hydrogenolysis
Ph
O
O
O Me
H2/cat. Pd(OH)2 HO EtOH/acetone OMe 92%
OH O Me
OMe
Deprotection(2)
Selectivity
Protection(2)
• Progress (4,6-, endo-2,3- and 3,4-O-benzylidene acetals) Ph
OMe OH OH O RO OR OMe OMe DMF/CSA 82% OO O RO OR OMe
Thermodynamic products, six membered ring (1,3-diol) are preferred Over five-membered rings (1,2-diols)