Diels-Alder reaction tetrodotoxin synthesis

Tetrodotoxin, a complex natural product containing several six-membered rings joined together, is a poison isolated from the ovaries and liver of the puffer fish, so named because the fish inflates itself into a ball when alarmed. Eating fish tainted with trace amounts of this potent toxin results in weakness, paralysis, and eventually death. One step in the synthesis of tetrodotoxin involves forming a six-membered ring by a Diels-Alder reaction. 

The Diels-Alder reaction forms new carbon-carbon bonds, so it can be used to synthesize larger, more complex molecides from smaller ones. For example. Figure 16.8 illustrates a Diels-Alder reae-tion used in the synthesis of tetrodotoxin. a toxin isolated from many different types of puffer fish. 

Lycopene, a highly unsaturated red pigment found in tomatoes, watermelon, and other fruits (Opener, Section 16.7) The Diels-Alder reaction and the synthesis of tetrodotoxin, a toxin isolated from the puffer fish (Section 16.12)... 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

An approach toward the synthesis of simple analogs of tetrodotoxin (115) (see also Sections VI,C and VIII) involved a Diels-Alder reaction between a butadiene and a pyrimidine derivative. Thus, butadiene and methyl orotate... 

A Diels-Alder reaction between 3-bromo-levoglucosenone and butadiene gives rise to adduct (10), which could be converted into (11), which represents the guanidinium part of tetrodotoxin. An interesting intramolecular Diels-Alder reaction (Scheme 3) was a key step in a synthesis of (+)-isovelleral (12) from the L-erythuronic acid derivative (13) which is accessible from D-ribonolactone. The synthesis produced firstly the diastereomer (14) of (-f-)-isovelleral (12), but the two were thermally interconvertible by an ene-type opening and closing of the three-membered... 

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