Chemo-Enzymatic Synthesis of 1’-Photoreactive Sucrose Derivatives via Ether Linkage

Abstract

As the 1'-hydroxyl group of sucrose is well known to be less reactive than other primary alcohols, there are no reports on the substitution of a phenoxy group at this position. Chemo-enzymatic synthesis of photoreactive 1'-phenoxy-substituted sucrose was examined to elucidate the functional analysis of sweet receptors.

Cosolvent-Promoted O-Benzylation with Silver(I) Oxide: Synthesis of 1′-Benzylated Sucrose Derivatives, Mechanistic Studies, and Scope Investigation

“…Initially, we wanted to prepare 1′-OH-heptaacetylsucrose 1 as a precursor for subsequent benzylation. To conveniently obtain compound 1 , we averted the tedious strategy by protection and deprotection and chose a more efficient enzymatic method involving the hydrolysis of commercially available octaacetylsucrose in the presence of alcalase. Next, sucrose 1 was reacted with p -(trifluoromethyl)­benzyl bromide 2a with Ag 2 O in CH 2 Cl 2 , which is the commonly used solvent in carbohydrates field (Table ).…”

Optimization of sucrose 1’-position modification with 3-(trifluoromethyl)diazirinyl benzylbromide derivatives for photoaffinity labeling

“…Although excess amounts of benzyl alcohol derivative (up to 10 eq) and Ag 2 O (up to 15 eq) were subjected to the reaction, no desired product was observed at any conditions (Table 1 Entries 1-4). To compare these synthetic conditions, the reaction with 1'-OH acetylsucrose 3 19,21,22 (0.075 mmol) and diazirinylbenzyl bromide derivative 5 20 (2 eq) in the presence of Ag 2 O (3 eq) was conducted in CH 2 Cl (5 mL). The 1'-O-diazirinyl benzyl substituted heptaacetyl sucrose 6 was afford less than 8% at 60 °C (Table Entry 5).…”

Asymmetric Synthesis of Photophore-Containing Lactisole Derivatives to Elucidate Sweet Taste Receptors

“…The three-membered azi (N=N) partial structure of trifluoromethyldiazirine is not stable for the Mitsunobu condition because the reactant, diethyl azodicarboxylate DEAD also has an azo group in its structure. The reaction with diazirinyl phenol derivatives and 1 -hydroxy peracetylsucrose with DEAD or Tsuda reagents did not occur in our previous study [14]. The synthetic plan was based on the preparation of trifluoroacetyl modified on the aromatic ring of lactisole; then we constructed a diazirinyl three-membered ring on the trifluoroacetyl group.…”

“…Three major photophores-phenylazide, benzophenone and (trifluoromethyl)phenyldiazirine-are used for photoaffinity labeling [11]. We reported several preparations of gustatory ligands to elucidate gustatory receptors [12][13][14][15][16][17][18][19][20]; however, there are few studies on the synthesis of photoreactive lactisole derivatives which have aimed to elucidate their biological activities. In this paper, we describe the comprehensive synthesis of photoreactive lactisole derivatives (Figure 1), which we then used in an inhibitory activity assay for cell-based human sweet taste receptors.…”