Thiourea natural products synthesis

Chiral H-bond donors and acids have proven their potential many times over several decades. Some useful apphcations in natural product synthesis have been reported, using either hydrogen bonding activation as the sole catalytically active principle, or utilizing bifunctional catalysts. With respect to the catalytic moiety of choice, the considerable potential of thioureas can be emphasized, especially those based on Cinchona alkaloids (Table 6). 

P-Amino carbonyl compounds containing an a-atkyUdene group are densely functionalized materials, which are widely applied in the synthesis of medicinal reagents and natural products [265]. These products are usually prepared through the classic aza-Morita-Baylis-Hillman reaction [176, 177] of activated imines and electron-deficient alkenes catalyzed by tertiary amines or phosphines. Chen and co-workers, in 2008, identified bis-thiourea 106 as a suitable catalyst for the... 

Development of amino thiourea catalysts as an artificial enzymes and their application to catalytic enantioselective synthesis of natural products and medical supplies 06Y1139. 

Since oxazolidines and oxazolidinones are fiindamental structural classes in organic chemistry (chiral auxiliaries) and in medicinal chemistry (e.g., Linezolid) and since they mask P-hydroxy-a-amino acids, which are widespread in various biologically active compounds and in natural products, the enantioselective synthesis of oxazolidinones is a challenging topic. Indeed, a new method for the direct synthesis of chiral 4-carboxyl oxazolidinones 168 by the catalytic asymmetric aldol reaction of isocyanato-malonate diesters 166 with aldehydes 167 in the presence of a thiourea catalyst (TUC) was developed. Since the resulting chiral 4-carboxy oxazolidinones are the equivalent of P-hydroxy-a-amino acids, this procedure... 

The synthesis of six-membered all-carbon rings have been extensively studied in the literature, mainly because of their importance as constituents in natural products and biologically relevant compounds. The first example of an enantioselective organocatalytic domino reaction with nitroalkenes to furnish cyclohexanes was disclosed by Takemoto and co-workers [38] in 2004. In this work, a domino Michael addition of 7,8-unsaturated-(3-ketoesters (58) to nitroalkenes (28) catalyzed by a bifunctional amino-thiourea (Takemoto s catalyst, XVIII) and 1,1,3,3-tetramethylguanidine (TMG) was reported with excellent results and diastereoselectivities (up to 71% yield, up to >99% ee) and was recently applied to the synthesis of (-)-epibatidine. 

The enantioselective, organocatalytic variant of the Petasis reaction, developed by Takemoto and coworkers from the University of Kyoto, represents a breakthrough in the synthesis of enantiopure 1,2-dihydroquinolines. As mentioned before, this structural unit is present in many natural products and biologically active compounds, and therefore an effective and short synthetic route via the Petasis-type reaction to enantiopure compounds in this class is a major leap forwards. Screening of the new thiourea catalysts in the Takamoto group resulted in a highly effective catalyst 13, specifically designed for the Petasis reaction. 

The final natural product that will be discussed herein to demonstrate the applicability of asymmetric organocatalysis to assemble the monoterpenoid part of indole alkaloids is (H-)-yohimbine (282) (Scheme 6.46). Yohimbine is a well-known monoterpenoid indole alkaloid that has been isolated from several natural sources and for which the first total synthesis dates back to the 1950s [140]. Two organocatalytic total syntheses of this important natural product have been reported recently by the groups of Jacobsen and Hiemstra [141,142], Jacobsen s synthesis of 282 commenced with the thiourea 170a-catalyzed acyl-Pictet-Spengler reaction between tryptamine 283 and the protected hydroxyaldehyde... 

By means oforganocatalytic methods, it is also possible to synthesize 2 H-azirines, which are the smallest heterocycle containing a C=N in a three-membered ring, and which occur in some natural products. For this purpose, the Neber reaction of several P-ketoxime sulfonates 16 catalyzed by thiourea 17 was carried out, giving the corresponding 2H-azirines 18 with good results (Scheme 27.6) [17]. This reaction was applied as a key step in the synthesis of the antipode of natural dysidazir-ine, which was achieved in five steps with 75% yield and 93% ee. 

Many of the most versatile and widely used syntheses of pyrimidines are straightforward examples of [3+3] condensations of amidines, guanidines, ureas and thioureas with 1,3-dielectrophiles, and clearly a considerable measure of control over the degree and nature of the substitution pattern in the final product is possible by appropriate choice of the two three-component units. Representative examples are given in equations (112)—(115), and the use of sulfamide in place of amidines, etc., allows the method to be extended to the synthesis of polyheteroatom systems e.g. equation 116). 

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