2/7-1 -Benzopyrans

The cataracts that can appear even in those diabetics whose disease is under control have been attributed to accumulation in the eye of sorbitol that results from the reduction of glucose by elevated levels of the enzyme aldose reductase that accompanies the disease. Inhibitors of that enzyme have been investigated as a means for controlling such cataracts. Known agents, as would be expected with enzyme inhibitors, tend to show marked differences in potency between optical isomers. The enantioselective synthesis of one of these compounds starts with the formation of an imine (12-3) of dihydrochromone (12-1) with the S form of the chiral 

A structurally unusual 3-blocker that uses a second molecule of itself as the substituent on nitrogen is included here in spite of the ubiquity of this class of compounds. Exhaustive hydrogenation of the chromone (13-1) leads to a reduction of both the double bond and the carbonyl group, as in the case of (11-2). The car-boxyhc acid is then reduced to an aldehyde (13-2) by means of diisobutylaluminum hydride. Reaction of that intermediate with the ylide from trimethylsulfonium iodide gives the oxirane (13-3) via the addition-displacement process discussed earlier (see Chapters 3 and 8). Treatment of an excess of that epoxide with benzylamine leads to the addition of two equivalents of that compound with each basic nitrogen (13-4). The product is then debenzylated by catalytic reduction over palladium to afford nebivolol (13-5) [16]. The presence of four chiral centers in the product predicts the existence of 16 chiral pairs. 

Coumarins (also called 2H-l-benzopyran-2-ones or 2-oxo-2H-chromenes) are common in nature and find their main applications as fragrances, pharmaceuticals and 

The Organic Chemistry of Drug Synthesis, Volume 7. By Daniel Lednicer Copyright 2008 John Wiley Sons, Inc. 

Migraine was a condition that was refractory to treatment until the discovery of the serotonin receptor blocker, such as sumatriptan. This agent was soon followed by several other drugs that acted by the same mechanism. Tidembersat (13) a compound more closely related, both in structure and mechanism of action, to antihypertensive benzopyrans that act on 

---

The now classical route to 2/7-1 -benzopyrans, cyclisation of aryl propargyl ethers, has been utilised in the synthesis of mollugin <06T8419> and to prepare novel photochromic naphtho[2,l-b]pyrans <06T737>. 

The electrophilic cyclisation of aryl 3-arylprop-2-ynyl ethers to 3,4-disubstituted 2/7-1-benzopyrans 13 is achieved efficiently using IC1, h or PhSeBr. The reaction is compatible with a wide range of substituents and the 3-iodo group offers potential for the elaboration of the system <07JOC1347>. 

Acetyl-5,7-dihydroxy-2,2-dimethyl-6-(3-methyl-2-butenyl)-2/7-1 -benzopyran, A-30028... 

Dihydro-1.4-benzodioxin 2,3-Dihydrobenzofuran 3,4-Dihydro-1/7 -2-benzopyran 3,4-Dihydro-2/7 -1 benzopyran 3,4-Dihydro-2W 1-benzopyran-2-one 2,3-Dihydro-4ffl-benzopyran-4-one... 

CA Index Name 2/7-1-Benzopyran-3-carboxylic acid, 7-hydroxy-2-oxo-... 

Hydroxy-2-oxo-2/7-1 -benzopyran-3-carboxylic acid Me ether, Et ester, in H-00426... 

Acetyl-7-hydroxy-4-methy 1-2/7-1 -benzopyran-2-one, A-00018 Alizarine red S Na salt, in A-00081... 

---