Streptazoline synthesis

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). 

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. 

The enantioselective total synthesis of streptazolin (609), a neutral lipophilic antibiotic isolated from cultures of Streptomyces viridochromogenes, utilizes a tandem iminium ion— vinylsilane cyclization of the tartrate-derived 607 together with intramolecular acylation as a way of achieving high stereoselectivity. Heating a mixture of 570 and ( )-4-bromo-4-(tri-methylsilyl)-3-buten-l-amine (605) followed by dehydration with acetyl chloride provides the imide (606) in reproducible yields of 90%. Reduction of 606 with sodium borohydride affords 607, which is refluxed in trifluoroacetic acid to provide, after careful purification, the single bicyclic adduct 608 in 74% yield. This is then transformed in four steps to the desired streptazolin (609) [196] (Scheme 134). 

A Heck-type ring closure, using formate as the reducing agent was used to form a five-membered ring and a stereodefined exo-cyclic alkene in a synthesis of streptazolin 5.166 (Scheme 5.46)." Another synthesis of this natural product may be found in Scheme 11.87. The mechanism of reduction by formate is shown in Scheme 5.50. 

Interestingly, the oxidation of the allylsiloxane 110 provided the allylic alcohol in 55% yield, however the conversion to 111 proved problematic. The synthesis was completed with the removal of the pivaloyl group in 111 followed by in situ carbamate formation to afford (+)-streptazolin (112) in 76% yield, which was converted to the crystalHne aUylic acetate 113 for characterization. 

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