Stemoamide

The stereoselective addition of the titanium enolate of A-acetyl-4-phenyl-l,3-thiazolidine-2-thione 153 to the cyclic A-acyl iminium ion 154 is utilized in the synthesis of (-)-stemoamide, a tricyclic alkaloid <06JOC3287>. The iminium ion addition product 155 undergoes magnesium bromide-catalyzed awtz-aldol reaction with cinnamaldehyde 156 to give adduct 157, which possesses the required stereochemistry of all chiral centers for the synthesis of (-)-stemoamide. 

A total synthesis of (—)-stemoamide is achieved from (—)-pyroglutamic acid using ruthenium-catalyzed enyne metathesis as a key step in 14 steps in 9% overall yield [Eq. (6.79)]... 

CH2CI2 at RT to give 84, which is converted into (—)-stemoamide via halolactonization. 

Reaction of the carbene complex 148 with alkyne affords vinylcarbene 150 via metallacyclobutene 149. In the intramolecular reaction of enyne 152, catalysed by carbene complex 151, the triple bond is converted to vinylcarbene 153 which then reacts with the double bond to give the conjugated diene 154. Generation of 154 is expected by the formation and cleavage of cyclobutene 155 as a hypothetical intermediate. Based on this reaction, Ru-catalysed intramolecular metathesis of enyne 156 gave the N-containing cyclic diene 157, from which (—)-stemoamide (158) was synthesiszed. The reaction can be understood by assuming the formation of the hypothetical cyclobutene 159 from 156 [52],... 

Stemoamide (36), isolated from the roots and rhizomes of Stemona tuberosa in 1992, is one of the structurally simplest members of the Stemona family and has shown many biological activities. Olivo and others used a highly... 

Intramolecular Diels-Alder reactions between oxazoles and acetylenes have also been used as a key step in a number of natural product syntheses. For example, cycloadducts 69 and 70 were derived from intramolecular Diels-Alder reactions of their respective acylic 2-substituted oxazole precursors. These cycloadducts were key intermediates in the syntheses of natural products (—)-stemoamide and (- -)-colchicine, respectively (Scheme 11) <2000JA4295, 2000T10175>. 

The total synthesis of polycyclic alkaloid (-)-stemoamide was achieved in the laboratory of M. Mori via a ruthenium carbene catalyzed enyne metathesis. The cyclization was effected by 5 mol% of catalyst in benzene at 50 °C. After 11h of stirring under these conditions, 87% of the 5,7-fused bicyclic system was formed. 

Kinoshita, A., Mori, M. Total Synthesis of (-)-Stemoamide Using Ruthenium-Catalyzed Enyne Metathesis Reaction. J. Org. Chem. 1996, 61, 8356-8357. 

Scheme 44. Ring-closing enyne metathesis using Grabbs catalyst for the synthesis of ( )-stemoamide.

An alternative method for preparing vinyl bromides can be incorporated into a synthesis of alkynes when combined with an E2 reaction. In Jacobi s synthesis of (-)-stemoamide,l aldehyde 196 was treated with... 

An RCM of an enyne giving a diene that is eminently suitable for elaboration into (-)-stemoamide has been reported. ... 

Ring closure metathesis (RCM) has been used in the cyclisation of 6 to give the pyrrolidinoazepine 7 <97SL1179>. This reaction has also been used to prepare the corresponding 5, and 6-membered systems. In an extension of this methodology, the ring closure of 8 to 9, has been used in the total synthesis of (-)-stemoamide 10 <97H(46)287>. 

Jacobi and Lee ° found P2O5 to be effective for preparing larger quantities (20 g) of an oxazole required for their synthesis of ( )-stemoamide. In this case, 2-(3-chIoropropyI)-5-methoxy-4-methyIoxazoIe 464 was prepared from 463 (Scheme 1.126). The authors found that 464 was sufficiently pure as isolated to prepare the acetylenic oxazole 465. 

Synthesis of Evodone Synthesis of Ligularone and Petasalbine Synthesis of Paniculide-A Synthesis of Gnididione Synthesis of Norsecurinine Synthetic Approach to Geigerin Synthesis of Stemoamide Thiofurans and Amidofurans... 

Jacobi and co-workers ° described the total synthesis of racemic stemoamide, a member of the stemona alkaloids isolated in 1992 from Stemona tuberosa, and an enantioselective route to (-)-stemoamide. The starting alkyne oxazoles 200 and 203 were prepared from y-chlorobutyryl chloride 199 in five steps (Fig. 3.60). 

Fortunately, when 203 was refluxed in diethyl benzene at 182°C, a 50-55% yield of butenolide 206 (the proposed precursor to stemoamide) was obtained directly. 

The synthesis was completed by reduction of 206 with the nickel boride catalyst derived from nickel(ll) chloride and sodium borohydride directly producing ( )-stemoamide in 73% yield. In addition, a 15% yield of the cfr-lactone 207, derived from a-face reduction of 206 followed by epimerization at C-10, was also obtained. 

An enantioselective synthesis of natural (-)-stemoamide was carried out precisely as described for the synthesis of racemic stemoamide. In this case, enantiomerically pure 203 was prepared from L-pyroglutamic acid in eight steps. 

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