Toxins total synthesis

And so the skillful selection, introduction, and removal of a total of 12 different protective groups have played a major role in the successful total synthesis of paly toxin carboxylic acid (Figure 1,2). 

Synthetic study on marine polycyclic ethers and total synthesis of hemibreve-toxin B 98YGK940. 

Photochemical equilibration of the 3 2 stereoisomeric mixture of N-acyl vinylogous ureas in DMF by irradiation at 300 nm in a Ray-onet reactor equipped with a stannous chloride filter solution at 37 °C for 4 h leads to a 6 1 mixture of trans-Aa b and c .v-Aa b paly-toxins. The total synthesis of palytoxin (1) is now complete. 

This lithiated epoxysulfone cyclisation strategy has been iteratively applied in the total synthesis of hemibrevitoxin B, a polycyclic ether marine toxin from the red tide organism Gymnodinium breve (Scheme 5.41) [64]. 

At this time, a solid phase automatic peptide synthesizer was acquired, so we attempted total synthesis of Sh I. A solid phase synthesis of Ax I (antho-pleurin A) had previously been reported in an abstract (36). The synthetic Ax I possessed only 11% of the toxicity of the natural toxin. 

A stereoselective total synthesis of dendrobatide toxin 251 D was developed by Overman et al.237) involving an epoxidation of the (S)-proline derivative (237) to furnish the oxirane (238) as major product. In their approach towards the total synthesis of the same natural product Thomas et al.238) investigated the stereoselectivity of the epoxide formation from (S)-5-acetylpyrrolidin-2-one and dimethyloxosulfonium methylide. A diastereoselectivity of d.s. 50-60% was achieved 238. ... 

The first total synthesis of a phallotoxin was that of norphalloin, the norvaline analogue of phalloidin.16 This synthesis, outlined in Scheme 2, initially involves the synthesis of two building blocks followed by their covalent binding via a tryptathionine moiety. Subsequent deprotection and coupling steps using classical methods of peptide synthesis results in the formation of norphalloin, which has proved to be even more toxic than the natural toxins. Since the synthesis of norphalloin, a number of synthetic analogues have been synthesized in order to obtain information on structure-activity relationships.[7 8]... 

Another highly versatile building block derived from diacetone-glucose 54 is the 1,2-acetonide of 3-C-methyl-a-D-allose in its furanoid form 57, which has been utilized as the key compound in a convergent total synthesis of ACRL Toxin I (63). Its elaboration from 54 starts with a pyridinium dichromate / acetic anhydride oxidation (64), is followed by carbonyl olefination of the respective 3-ulose with methyl (triphenyl)phosphonium bromide and hydrogenation (— 55 56), and is completed by acid cleavage of the 5,6-isopropylidene group. This four-step process 54 -> 57, upon optimization of reaction conditions and workup procedure, allows an overall yield of 58 % (63), as compared to the 22 % obtained previously (65). 

The utilization of the furanoid 3-C-methyl-D-allose building blocks 57 and 60 for a convergent total synthesis of ACRL Toxin I in the form of its stable 3-0-methyl ether (63) involved their conversion into enantiomerically uniform connective segments. The key feature of the retrosynthesis was the expectation... 

An interesting application of this protocol was utilized in the total synthesis of ( )-pumiliotoxin.82 Intramolecular acylation of the a-anion of vinyl sulfone 128 gave enaminone 129 which was readily converted to the desired alkaloid pumilio-toxin 130 (Scheme 35). 

AM-Toxin. The pathogen Alternarla mall causes leaf spot disease of apple and produces necrotic spots on fruits, leaves, and shoots of susceptible cultivars. AM-toxIn [18], a host-specific toxin, and several related toxins are responsible for these symptoms and their structures have been elucidated and confirmed by total synthesis 1101-1031. 

White, J.D, Blakemore, P.R., Browder, C.C., Hong, J., Lincoln, C.M., Nagorny, PA., Robarge, L.A., and Warthop, DJ. 2001. Total Synthesis of fiie Marine Toxin Polycavemoside A via Selective Macrolactonization of a Trihydroxy Carboxylic Acid. Journal of the American Chemical Society 123(35), 8593-8595. 

Danishefsky and coworkers have demonstrated the conversion of lactones to carbocycles by the 3,3-sigmatropic shift of silylketene acetals. Jq the total synthesis of the Fusarium toxin equisetin, for example, keto lactone (138) was converted to its bissilyl derivative (139) by reaction with 2 equiv. of LDA and an excess of TMS-Cl. In situ thermolysis of ketene acetal (1 ) led to a very smooth transformation into ester (140), which was carried on to equisetin (Scheme 26). This methodology was also applied by Schreiber and Smith in the preparation of the cyclohexyl moiety of the immunosuppressive agent FK-506. Ireland-Claisen rearrangement of silylketene acetal (142), prepared by treatment with TBDMS-OTf and triethylamine at low temperature, provided, after hydrolysis of the silyl ester, the carboxylic acid (143) in 71% overall yield (Scheme 27). The strict translation of configuration via a boatlike transition state is typical for this permutation. 

Some examples of research under development include a synthetic conjugated polysaccharide vaccine against Haemophilus influenzae type B, which has been described in 2004 (O Fig. 34). The vaccine prototype was obtained by conjugation to human serum albumin (HSA) [173]. Furthermore, very recently a malaria vaccine has been suggested [174] which is based on the total synthesis of the malaria toxin responsible for the morbidity and mortality associated with malaria. The malaria parasite expresses a large amount of glycosylphosphatidylinositol... 

The total synthesis of pederin, a potent insect toxin was achieved by T. Takemura and co-workers. One of the key steps of the synthesis was an intramolecular samarium diiodide induced Reformatsky reaction to construct the lactone subunit of the molecule. The transformation was carried out in tetrahydrofuran at 0 °C without the use of additives or catalysts. 

The first total synthesis of the marine polycyclic ether toxin (-)-gambierol was accomplished in the laboratory of M. Sasaki. The introduction of the a,(3-unsaturation into the seven-membered H ring of the FGH tricyclic subunit proved to be problematic, because both the conventional selenium-based method and the Nicolaou oxidation with IBX failed. However, when the seven-membered ketone was treated with LiHMDS in the presence of TMSCI and EtsN, the corresponding silyl enol ether was formed, which was oxidized under Saegusa conditions to give the desired cyclic enone in high yield. Because of the small scale of the reaction, a large excess of Pd(OAc)2 was used in acetonitrile so the presence of a co-oxidant was not necessary. 

The total synthesis of the marine toxin polycavemoside A was achieved by J.D. White and co-workers. In order to couple the central pyran moiety in a Nozaki-Hiyama-Kishi reaction, the aldehyde side chain had to be first homologated to the corresponding terminal alkyne and subsequently transformed into a vinyl bromide. The aldehyde substrate was treated under the Ohira-Bestmann protocol, and the desired alkyne product was obtained in high yield. 

Takemura, T., Nishii, Y., Takahashi, S., Kobayashi, J. i., Nakata, T. Total synthesis of pederin, a potent insect toxin the efficient synthesis of the right half, (+)-benzoylpedamide. Tetrahedron 2002, 58, 6359-6365. 

The desirability of having relatively copious quantities of the milk toxins for studies regarding their carcinogenicity, prompted Buchi and Weinreb139, 145 to develop a total synthesis of these metabolites. Notably, the only difference between aflatoxin Mi (13) and aflatoxin Bj (1) is the presence of the tertiary and benzylic hydroxyl functionality at C-14. Unfortunately, the methodologies utilized in the constructions of the toxins previously discussed are not applicable to this problem in that they inherently do not contain the necessary provisions for the initial presence, or the delayed introduction, of this C-14 hydroxyl. Therefore, a radically different approach was essential, which would provide for this contingency. 

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