Strigol synthesis

In preparation for scale-up of the strigol synthesis described by Sih (8), efforts were made to improve the yield of some of the seven steps involved in the scheme. Of these steps, nine are satisfactory from the standpoint of yield and experimental conditions. For three of the steps, we have improved the yield and/or experimental conditions such that the yield of (+ )-strigol would be raised to 2.85% overall from citral rather than 1.53% based on Sih s procedure and reported yields. Improvements were developed preparation of a-cyclocitral (III), the oxidation of the hydroxyaldehyde (V) to the ketoacid (VII), and for the preparation of the hydroxybutenolide (XVII). For the remaining five steps, our attempts to change experimental conditions have failed to improve, and in most cases to even obtain, the yields reported in the literature (8). We have considered the preparation of strigol analogs and determined the conditions and limitations for the preparation of a series of alkoxybutenolides (XVI) and a butenolide dimer (XVIII). Modification of the literature procedure (11) to eliminate the use of the mesylate (XX) and the use of polar aprotic solvents gave better yields of the 2-RAS (XXI). 

Finally, the number of steps in the strigol synthesis could be reduced by the direct conversion of Xa to Xlla. To this end, Xa was treated with 1.2 equivalents of NBS in refluxing carbon tetrachloride under the irradiation of a 150-watt lamp. Purification of the crude product mixture by thin layer chromatography afforded two products Ila (27%) and the unanticipated bromoketone XV (31%). The reaction... 

With the A-ring unit readily available, we directed our attention to the formation of the B-ring. At first, we duplicated the five step scheme reported in Sih s strigol synthesis involving 1) esterification of the acid 14, 2) allylic bromination with N-bromo 8 ucc i n imi d e (NBS) to 15, 3) condensation with the sodium salt of dimethyl malonate to 16, 4) alkylation with methyl bromoacetate to 17, and 5) acid catalyzed hydrolysis and decarboxylation to the acid 18. 

Strigol synthesis has been completed by both Brooks and Pepperman using the new or improved procedures. 

Scheme IX. Dolby s partial strigol synthesis. Preparation of the hydrindan 15.

The availability of diketoacid 10 from our strigol synthesis prompted us to examine synthetic entry to A-B-D ring analogs. Following the esterification process used for 23, we found that the acid 10 could be similarly esterified with bromobutenolide 15 and bromophthalide 34 to provide the analogs 39 (41%) and 40 (70%) respectively... 

Total synthesis of ( +)-strigol was reported in 1974 by Sih and co-workers (7 ) and the details of their scheme and resolution of (i)-strigol was reported in 1976 (8). Raphael and co-workers reported the synthesis of strigol by a different method also in 1974 (9) and 1976 (10). 

DAILEY AND VAIL An Improved Partial Synthesis of ( )-Strigol... 

The excellent total synthesis of strigol developed by Sih and co-workers (7) formed the basis for our efforts to devise an improved synthesis. The general synthetic plan involves consecutive A+B+C+D-ring formation as shown. 

The structure of strigol is shown above with the rings identified as A, B, C, and D for further reference. Because the total synthesis of the compound for the production of even small amounts has proven to be exceedingly difficult, it is estimated that only about five grams of pure material had been isolated prior to 1984. 

Reizelman, A. Zwanenburg, B. Synthesis of the germination stimulants ( )-orobanchol and ( )-strigol via an allylic rearrangement. Synthesis 2000, 1952-1955. 

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