Tricyclic compound preparation from iodide

Travoprost is an isopropyl ester of fluprostenol, which shows an lOP-reducing effect as potent as latanoprost [69], The synthetic route of travoprost 31 is shown in Scheme 4 [70], The cleavage of the three-membered ring of tricyclic ketone 26 by the attack of the cuprate prepared from vinyl iodide 25 gave the compound 27. 

Fig (16) The enone (131), prepared from (130) is alkylated with iodide (133) to obtain the product (134). It reacts with trimethylsilyl cyanide and zinc iodide. The resulting product (135) is converted to tricyclic compound (136) by heating with hydrochloric acid and ethanol. 

From alcohols. Alcohols can be transformed into phenylselenides in a stepwise manner via mesylation and reaction with lithium phenylselenolate. This procedure offers obvious advantages over the formation of the corresponding bromides or iodides when subsequent reaction with strong nucleophiles, such as organolithium compounds, are necessary to prepare the radical precursors. The diol 8 is converted to the bis(phenylselenide) 9 via the corresponding bis(mesylate) as shown in Scheme 2 [6]. Compound 9 is converted to the radical precursor 11 via reaction with lithium phenylacetylide followed by alkylation with allylbromide and a Pauson-Khand reaction. Such a reaction sequence would not be feasible with an alkyl halide. The cyclization afforded the expected tricyclic compound 12 in 95% yield. 

An ester of alanine with an arylaliphatic alcohol has shown promise as a non-tricyclic antidepressant. It may be speculated that the hindered milieu of the ester linkage protects the compound from hydrolysis by endogenous esterases. The preparation starts by reaction of pheny-lacctate 83 with methyl magnesium iodide to give tertiary carbinol 84. Acylation with 2-bromo-]>ropionyl bromide leads to ester 85 displacement of halogen with ammonia leads to alaproclate ( 6) [211. 

Ley reported that selenium promoted carbocyclization reactions can also be effected by the enolic olefinic bonds of -dicarbonyl compounds [111]. These reactions occur with N-PSP in the presence of zinc iodide, tin tetrachloride or aluminium trichloride. An example is reported in Scheme 33. In the intermediate 219, derived from the -ketoester 218, cyclization through the oxygen atom to afford 220 is kinetically favoured. This reaction, however, is reversible, and upon prolonged reaction times and in the presence of strong acids the carbocyclization product 221 is formed. This procedure has been recently employed by Ley to effect the conversion of the alkenyl p-keto lactone 222 into the tricyclic selenide 223 (Scheme 33) which is a key intermediate in the preparation of model compounds with antifeedant activity [112]. 

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