“…Given the apparent sensitivity of various chitinases to modifications of the allosamidins, we embarked on the synthesis of analogs 64 − 66 . The synthesis of several other allosamidin analogs have recently been reported in the literature. − 2 Structures of potential chitinase inhibitors.…”
Section: Development Of the Ses Azaglycosylation Methodsmentioning
Allosamidin, recently isolated from mycelial extracts of
Streptomyces sp. 1713, is a powerful and
selective
chitinase inhibitor. The total synthesis of allosamidin is
described herein. The electric eel
acetylcholinesterase-mediated enantioselective hydrolysis of
(trans,trans)-2-(benzyloxy)cyclopentene-1,3-diol
diacetate accessed a
monoacetyl derivative. Five additional steps produced a protected
version of the aglycon (“allosamizoline”) sector
of allosamidin. An allal derivative stereoselectively reacted with
benzenesulfonamide in the presence of a halonium
source to afford a 2β-halo-1α-sulfonamidohexose. Treatment of
this product with a strong base generated an
intermediate 1,2-sulfonylaziridine, which was trapped with a protected
allal derivative to provide a disaccharide
glycal. Reiteration of this scheme gave access to the required
trisaccharide. Following deprotection, the total
synthesis
of allosamidin was accomplished. In addition, the method, with
modification, gave access to several allosamidin
analogs.
“…Given the apparent sensitivity of various chitinases to modifications of the allosamidins, we embarked on the synthesis of analogs 64 − 66 . The synthesis of several other allosamidin analogs have recently been reported in the literature. − 2 Structures of potential chitinase inhibitors.…”
Section: Development Of the Ses Azaglycosylation Methodsmentioning
Allosamidin, recently isolated from mycelial extracts of
Streptomyces sp. 1713, is a powerful and
selective
chitinase inhibitor. The total synthesis of allosamidin is
described herein. The electric eel
acetylcholinesterase-mediated enantioselective hydrolysis of
(trans,trans)-2-(benzyloxy)cyclopentene-1,3-diol
diacetate accessed a
monoacetyl derivative. Five additional steps produced a protected
version of the aglycon (“allosamizoline”) sector
of allosamidin. An allal derivative stereoselectively reacted with
benzenesulfonamide in the presence of a halonium
source to afford a 2β-halo-1α-sulfonamidohexose. Treatment of
this product with a strong base generated an
intermediate 1,2-sulfonylaziridine, which was trapped with a protected
allal derivative to provide a disaccharide
glycal. Reiteration of this scheme gave access to the required
trisaccharide. Following deprotection, the total
synthesis
of allosamidin was accomplished. In addition, the method, with
modification, gave access to several allosamidin
analogs.
“…Although the C-3 hydroxyl group of the terminal nonreducing unit of allosamidin ( 4 ) can possibly hydrogen bond to Asn45 helping to enhance binding, the unique configuration of the sugar units in this inhibitor may well serve to modify its selectivity profile (compared to the glucoallosamidins, for example) or, more intriguingly, play a role in lessening the likelihood of the inhibitor being recognized as a substrate by N -acetylglucosaminidases and degraded. Pseudotrisaccharide 416 , an “ all - gluco ” analogue of allosamidin ( 4 ), is apparently susceptible to hydrolysis by chitinases themselves (Table ) . That the C-3 hydroxyl group of the central sugar in allosamidin ( 4 ) might mimic an incoming nucleophilic water molecule, as has previously been suggested, seems a less plausible explanation: the glucoallosamidins ( 286a and 286b ), both of which contain a central d -glucosamine unit rather than d -allosamine, are better inhibitors of certain chitinases than allosamidin ( 4 ) itself, and the “ all - gluco ” analogue 418 of demethylallosamidin shows activity 108 comparable to that of the natural compound 284 toward Candida albicans chitinase (see Table ).…”
Section: F Biological Activitymentioning
confidence: 99%
“…Takahashi and co-workers 115 have achieved the synthesis of the pseudotrisaccharide analogue 416 wherein the D-allosamine moieties of allosamidin ( 4) are replaced by N-acetyl-D-glucosamine units. This analogue is thus also related to the natural glucoallosamidins 286a and 286b (see Chart 14), both of which feature a central glucosamine unit flanked by N-acetylallosamine and allosamizoline moieties (Scheme 63).…”
“…Pseudotrisaccharide 416, an "all-gluco" analogue of allosamidin (4), is apparently susceptible to hydrolysis by chitinases themselves (Table 3). 115 That the C-3 hydroxyl group of the central sugar in allosamidin (4) might mimic an incoming nucleophilic water molecule, as has previously been suggested, 25 seems a less plausible explanation: the glucoallosamidins (286a and 286b), both of which contain a central D-glucosamine unit rather than D-allosamine, are better inhibitors of certain chitinases than allosamidin (4) itself, 95 and the "all-gluco" analogue 418 of demethylallosamidin shows activity 108 comparable to that of the natural compound 284 toward Candida albicans chitinase (see Table 3).…”
“…allosamidin analogue), which was stereo-selectively synthesized by the coupling reaction of disaccharide thioglycoside building block and allosamizoline 2 derivative building block 15 . The solid-liquid phase synthesis of compound 9 was also investigated (Scheme 1) 30 .…”
The pseudo-trisaccharide allosamidin 1 is a potent inhibitor of all family-18 chitinases, and it is confirmed to have insecticidal and antifungal activities. But the synthesis of allosamidins is very difficult, and it is a challengeable subject. Allosamidins were synthesized in solid-liquid phase, total solid-phase and total liquid-phase, respectively. Solid-liquid phase method realizes the partial solid-phase synthesis of allosamidins. Total solid-phase method greatly simplifies the purification process. Total liquid-phase method shortens the synthetic steps of allosamidins. The insecticidal and antifungal activities of allosamidins were also reported herein.
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