29 An Improved Partial Synthesis of (±)-Strigol OLIVER D. DAILEY, JR., and SIDNEY L. VAIL
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Southern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, New Orleans, LA 70179
Ethyl 3-hydroxy-2,6,6-trimethylcyclohex-1-ene-1carboxylate (Xa) has been prepared i n four steps from ethyl 4-OXO-2,6,6-trimethylcyclohex-2-ene-1-carboxylate ( I I I ) , readily obtained by the condensation of mesityl oxide and ethyl acetoacetate. Compound Xa can be incorporated in the Sih synthesis of (+)-strigol ( J . Am. Chem. Soc., 1976, 98, 3661), and its preparation offers a s i g n i f i c a n t improvement over existing methodology i n terms of lower cost of s t a r t i n g materials and reagents and a p p l i c a b i l i t y to large scale synthesis. Several routes from I I I to Xa were investigated, and notable results obtained in these approaches are discussed. F i n a l l y , the conversion of Xa to the hydrindan XIII is described.
(+)-Strigol ( I ) , isolated from cotton root exudates, is a very e f f e c t i v e germination stimulant for witchweed [e.g. Striga a s i a t i c a (L.) Kuntze] seed (1). Structure I depicts the r e l a t i v e
This chapter not subject to U.S. copyright. Published 1985, American Chemical Society
Thompson; The Chemistry of Allelopathy ACS Symposium Series; American Chemical Society: Washington, DC, 1985.
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THE CHEMISTRY OF ALLELOPATHY
stereochemistry of natural s t r i g o l but the absolute configuration has not been determined. The p a r a s i t i c weeds of Striga species are thought to germinate primarily i n response to a chemical signal from the host plant. Corn, r i c e , sugarcane, and sorghum are the major crop plants affected by Striga (2). However, the structure of the germination stimulant exuded from their roots remains unknown. Three t o t a l syntheses (3,4) of (+)-strigol have been reported i n the l i t e r a t u r e . Of these the Sih approach (3), using c i t r a l as starting material appears to be the most applicable to large-scale preparation. Several p a r t i a l syntheses of (+)-strigol have been reported, offering alternative approaches to intermediates i n the Sih synthesis (5-7) or improvements i n individual steps (8,9). Most recently, Brooks (7) has reported the synthesis of methyl 3-oxo2,6,6-trimethylcyclohex-l-ene-l-carboxylate ( l i b ) i n f i v e steps from α-ionone i n 48% o v e r a l l y i e l d , and other investigators have reported the one-step preparation of the corresponding acid l i e from a mixture of or- and 3~cyclocitrals (9).
l i a , R = CH CH. 2
b, R =
CH
3
c, R = H
To date, probably less than five grams of (+)-strigol has been synthesized. For extensive f i e l d studies, a large quantity ( i n excess of 100 g) w i l l be required. Although three t o t a l syntheses and several p a r t i a l syntheses of s t r i g o l have been reported, the need for a synthesis adaptable to large scale preparation s t i l l e x i s t s . The goal of the present study is to achieve a preparation of s t r i g o l , suitable for large-scale production, based upon inexpen sive starting materials and reagents and requiring a minimum of chromatographic p u r i f i c a t i o n . Results and Discussion Preparation of the Starting Material I I I . The starting material u t i l i z e d i n these investigations directed toward an improved p a r t i a l synthesis of (+)-strigol is ethyl 4-oxo-2,6,6-trimethyl-cyclohex-2ene-l-carboxylate ( I I I , Scheme I ) . This compound possesses the methyl groups and ester functionality i n the appropriate positions for elaboration to s t r i g o l according to the Sih route starting with the key intermediate e t h y l 3-hydroxy-2,6,6-trimethyl-cyclohex-l-enel-carboxylate (Xa). Compound I I I has been prepared by the zinc chloride or boron t r i f l u o r i d e catalyzed condensation of mesityl oxide with ethyl acetoacetate (10,11) or by the boron t r i f l u o r i d e catalyzed condensation of ethyl acetoacetate with acetone (11,12). These reactions give a product mixture of III and IV with III as the major product. In addition, isophorone has been isolated as a product (10). Presumably, isophorone is formed by the preferential
Thompson; The Chemistry of Allelopathy ACS Symposium Series; American Chemical Society: Washington, DC, 1985.
DAI LEY AND VAIL
An Improved Partial Synthesis of
(±)-Strigol
CH, ,COyCH CH t
:J
ZnCltoluene, heptane, Δ
O^CH,
CH, CH,
CH, CH,
CH, CH,
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