Streptazoline

The palladium-catalyzed cyclization reaction was used in the syntheses of several natural products such as siccanin [86], streptazolin [87], and ceratopi-canol (through a diyne, diene cascade) [80]. The production of the streptazolin precursor 149 through reductive cyclization of 150 is illustrative of the complexity that the reaction can provide (Eq. 29) [87]. 

Kibayashi and co-workers103 implemented the palladium-catalyzed cycloisomerization reaction in a stereoselective total synthesis of enantiomerically pure (+)-streptazolin. The cycloisomerization of enyne 172 to provide diene 173 was remarkably selective when performed in the presence of A,Ar -bis(benzylidene)ethylenediamine (BBEDA) as a ligand and water as a proton source (Scheme 44). 

Iminium ion-vinylsilane cyclizations closely related to the one described here have been used to prepare indolizidine alkaloids of the pumiliotoxin A and elaeokanine families, indole alkaloids, amaryllidaceae alkaloids, and the antibiotic (+)-streptazolin. The ability of the silicon substituent to control the position, and in some cases stereochemistry, of the unsaturation in the product heterocycle was a key feature of each of these syntheses. 

A related sequence was used by Kozikowski and Park (74) to prepare the ring skeleton of streptazolin (200), a compound that exhibits antibacterial and antifungal effects. In this approach, the tricyclic isoxazoline intermediate 198 was formed in the key cycloaddition step (Scheme 6.86). Thus, the reaction of oxime 197 (obtained from 4-piperidone) with sodium hypochlorite-triethylamine afforded tricyclic isoxazoline 198 in very good yield. This cycloadduct was converted to p-hydroxyketone 199 by reduction/hydrolysis using Raney Ni in the presence of acetic acid. Racemic streptazolin (200) was obtained from 199 in several additional steps (74). 

The structure of streptazolin (1> was established both spectroscopically and through chemical degradation studies. That the absolute configuration is 2a5.3S,7hV was shown with the use of Naka-wv/i/Y chiral dibenzoate method on the degradation product 2 as well as b> X-ray structural analysis3 of 0-acetvldihydrosirepla/olin (3). 

Streptazolin (1) shows limited antibacterial and fungicidal activity and influences the incorporation of thymidine in mouse spleen lymphocytes. 

A stable tricarbonyl-(r 4-l,3-diene)-iron complex is formed22 This causes the 1,4-diene 14-Z to isomcrizc to 1,3-dicnc 16, which in turn leads to the hexahydro l//-pyrindine present in streptazolin (1). 

Thus, (Z)-(+j-streptazolin (1) has been prepared stereoselectively in 17 steps with an overall yield of 2.2 - starting from L-tartaric acid (4). 

In the penultimate step of a synthesis of the unstable antibiotic Streptazolin, an iron tricarbonyl group co-ordinated to a 1.3-diene unit and two benzyl ethers were severed simultaneously using tribromoborane at -90 °C [Scheme 4.148].274 Tribromoborane has also been used to deprotect a phenolic benzyl ether in the presence of two phenolic methyl ethers in a synthesis of the alkaloid Lythrancepine [Scheme 4.149].275... 

Kozikowski, A. P., Park, P. U. Synthesis of streptazolin use of the aza-Ferrier reaction in conjunction with the INOC process to deliver a unique but sensitive natural product. J. Org. Chem. 1990, 55, 4668-4682. 

A simple example is the synthesis of analogues of the antibiotic and antifungal streptazolin by Cossy.40 Enantiomerically pure diene carbamate 188, prepared from the chiral pool (see chapter 23 and the workbook for this chapter) was treated with the Grubbs catalyst to form the six-memberedring 189 required for (-)-4,5-dihydrostreptazolin 190. This metathesis product inevitably contains a Z-alkene. 

The synthesis ofbestatin The synthesis of(+)-laurencin Streptazolin from tartaric acid Amino Alcohols... 

Vinylsilanes and enol ethers are also useful as ir-nucleophiles. A vinylsilane cyclization is an important step in a synthesis of (-i-)-streptazoline from tartaric acid (equation 68)." This reaction also nicely illustrates the high trans stereoselectivity of cyclization with respect to the C-4 oxygen substituent." The use of enol ethers is exemplified by two special cases (equations 69 and 70). The keto amide (103) is converted into tetracyclic (104) in a one-pot procedure involving (105) as a key intermediate. " A remarkable process is the quantitative cyclization of enone (106), despite the low nucleophilicity of an enone double bond (equation 70)." The most likely mechanism involves enol ether (107). It must be added that the conditions, saturated methanolic HCl, are crucial for the success of this reaction. 

Streptazolin (69) was first isolated from a culture of Strepfomyces... 

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