62501-67-1

Upstream product

• 62501-66-0 (2S)-3-(2'-benzyloxyphenoxy)-1,2-propanediol acetonide 
• 6272-38-4 O-benzylcatechol 
• 23788-74-1 (R)-2,2-dimethyl-1,3-dioxolane-4-ylmethyl p-toluenesulfonate 
• 100-44-7 benzyl chloride 
• 120-80-9 benzene-1,2-diol 

Downstream Products

• 62501-69-3 (2S)-3-(2'-hydroxyphenoxy)-1,2-propanediol ditosylate 
• 77133-43-8 (S)-WB-4101 
• 62501-70-6 (R)-(2,3-dihydrobenzo[b][1,4] dioxin-2-yl)methyl 4-methylbenzenesulfonate 
• 46049-49-4 (S)-(2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanamine 
• 753022-26-3 (S)-3-(2-hydroxyphenoxy)-1,2-bis(mesyloxy)propane 
• 62501-68-2 (2S)-3-(2'-benzyloxyphenoxy)-1,2-propanediol ditosylate 

Relevant academic research and scientific papers

Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2 alkylaminomethylbenzodioxans, competitive α adrenergic antagonists

The optical isomers of α-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3-(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzoloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the α-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine.

Structure-affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101

A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the α1a-AR with respect to the other two α1 subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the α1a-AR, α1b-AR, α1d-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific α1a affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high α1a affinity of (S)-1 and its α1a versus α1b selectivity slightly increasing the α1a/α1d and α1a/5HT 1A affinity ratios. The SAR data were evaluated in the light of known α1 subtype pharmacophores and of the α1a-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models.