1,2:5,6-Di-O-cyclohexylidene-3-C-methyl-α-D-allofuranose and other branched-chain analogues

Abstract

The reactions of 1 ,2 : 5,6d i -0cyc I o h exy I i d e n ea -D -rib0 -3h exof u ra n 0s u I o se with met h y I mag n es i u m bromide a n d with methyl-lithium yield the same 3-C-methyl derivative ; the configuration of this compound was established by preferential hydrolytic removal of the 5.6-O-cyclohexylidene residue, oxidative removal of C-6 with periodate, and a co n s i d e r a t i o n of the pro pert i es of t h e i so I a ted prod u c t, 1 ,2 -0 -c yc I o h exy I id en e -3 -Cm e t h y I -Q -D -rib0 -p e n t o d i a I d ofuranose, in comparison with those of 1,2-O-cyclohexylidene-a-D-~ibo-pentodialdofuranose and the dimer of 1.2-O-cyclohexylidene-a-D-xylo-pentodialdofuranose. The configuration of the products obtained by the reactions of ethyl-, vinyl-, phenyl, and 1 -naphthyl-magnesium halides and of phenyl-lithium with 1,2:5,6-di-U-cyclohexyli d e n ea -D -rib0 -3 -h exof u r a n 0s u I 0 s e is d i sc u ss ed .THE action of Grignard reagents and of organolithium compounds on the increasing range of now readily available oxo-sugars 1 has provided a convenient means of preparing a range of C-2 and C-3 branched-chain sugar^.^-^ Alternative synthetic procedures which have led ultimately to the formation of this group of sugar derivatives include the action of dia~omethane,~ sulphur ylids,6 or phosphoranes on the appropriate oxo-sugar. On the one hand these studies have led to a confirmation of structure of naturally occurring branched-chain monosaccharides,8 and on the other they have posed interesting problems with regard t o the factors which control the stereoselectivity of such reactions. For example, the action of Grignard reagents and of organolithium compounds on certain oxo-sugars has been found to

Analogues of nucleotides and oligonucleotides featuring difluorophosphonate, difluorophosphonothioate and difluorophosphinate functional groups

“…Thus, when difluoroalkenes 76a or b were reacted with hypophosphorous acid sodium salt 55b in the presence of triethylborane and air, a complete consumption of the substrates occurred and adducts 77 were isolated as a single diastereomer in each case (Scheme 17) [38]. Despite the smaller size of the reacting radical (when compared to phosphonyl and phosphonothioyl radicals), the stereodirecting effect of the 1,2-acetonide unit proved efficient in blocking the concave face of the ribofuranose [15,38]. Transforming adduct 77a into phosphite 78 and interaction with oxygen (air) or sulfur afforded protected phosphonic acid 79 and phosphonothioic acid 80, respectively, in the form of their solid, disodium salts (86% and 59% isolated yield, respectively) [39].…”

“…As this last step would probably play a crucial role in installing the requisite configuration on carbon C 3 0 , it was decided to start from a furanose derivative featuring a hindered a-face to force the hydrogen quenching to occur on the b-face (thereby positioning the phosphonodifluoromethyl unit on the desired face of the cycle), and to introduce the base in a subsequent step. Glucofuranose derivative 12 was chosen as a readily available substrate, because of the 1,2-dimethyl acetal protection and the known steric hindrance generated by the angular methyl group (Scheme 2) [15]. Oxidation of the C 3 0 hydroxyl group with Dess-Martin periodinane resulted in a clean and smooth production of ketone 13, which was subjected to the action of the anion of diethyl difluoromethylphosphonate [16].…”

Opiate Analgesics' Dual Role in Firefly Luciferase Activity

“…Opiates are known for their prototypical analgesic and pharmacological importance ( , ). It is observed that opiates inhibit either the basal () or neurostimulated increase in the adenylate cyclase activity in several mammals ( − ) and cause respiratory depression () due to their action on the brain stem respiratory centers. Owing to their immense importance in biochemical studies, the concept of opioid receptor was first postulated by Beckett and Casy (), and subsequently, Portoghese and co-workers () proposed different opiate receptors for structurally different opioids.…”