Shapiro synthesis

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

Shapiro published a critical analysis of the availability of the nucleobase cytosine on the primeval Earth in the highly-regarded Proceedings of the National Academy of Science (Shapiro, 1999). Some biogeneticists still believe that all the substances necessary for the synthesis of a nucleic acid were available in the much-cited (but hypothetical) primeval soup . Shapiro directs these optimists to the following problems ... 

About 40 different sugars are formed. Those required for nucleic acid synthesis, ribose and deoxyribose, are obtained in yields of less than 1%. It is completely unclear whether these could have been separated from the others under primeval Earth conditions (Shapiro, 1988). 

How could such difficulties be avoided Shapiro lists minerals which could have served either as the first replicators or as highly selective polymerases. He also considers a further possibility life may have begun as a metabolic network of reactions which involved monomers the replicators may have evolved in a later evolutionary phase. The misgivings mentioned, and the open questions referred to in earlier chapters, indicate that a de novo synthesis of RNA under the conditions present on the young Earth was almost impossible. Thus, models were and are being looked for which could bypass as many as possible of the problems referred to. 

An elegant application of the catalytic Shapiro reaction has been found in the synthesis of the natural product 129 (equation 45), a component of the sex pheromone of the summer fruit tortrix moth (Adoxophyes orana). ... 

During an investigation of the synthesis of oxazole-4-carboxylates, Shapiro reported that chlorination of amino[(phenylthio)methyl]malonate derivatives 91 with A -chlorosuccinimide (NCS), followed by treatment with Hunig s base, afforded the oxazolines 93. The oxazolines 93 were then converted to the respective oxazole-4-carboxylates 94-97 through decarbomethoxylation and elimination of thiophenoxide in the presence of methyl iodide. Methyl iodide traps the ejected thiophenoxide that would otherwise demethylate the oxazole-4-carboxylate (Scheme 8.31). " ... 

The bases of nucleic acids can also be considered prebiotic compounds. A possible prebiotic route to adenine has been described (Oro, 1960 Ord and Kimball, 1961 1962 see also Shapiro, 1995), as shown in Figure 3.4. For details see also Miller s review (Miller, 1998). Guanine, and the additional purines such as hypoxan-thine, xanthine, and diaminopurine could also have been synthesized by variations of the above synthesis (Sanchez et al, 1968). 

Lorenz Shapiro Stern Becker 7. Org. Chem. 1963, 28, 2332 Neumann Hillgartncr Synthesis 1971, 537. Hoffmann Michael Chem. Ber. 1962, 95, 528. 

Shapiro and co-workers have described [89] (in a paper submitted just before the death of this pioneer in the field of glycosphingolipid synthesis — for a review of his extensive work in this area see Ref. [1]) a synthesis of the thio-analogue (88) of glucosyl ceramide (and the saturated derivative) from 2,3,4,6-tetra-0-acetyl-l-mercapto- 3-D-glucopyranose (86) and the 1-deoxy-l-iodoceramide derivative (85) in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene. The product (87) was deacylated with methano-lic barium methoxide to give (88). 

It was first synthesised by Shapiro in 1973 (for a review see Ref. [1]) and recently several syntheses of the oligosaccharide portion have been described using modem methods of glycoside synthesis. 

Shapiro, R. 1984. The improbability of prebiotic nucleic acid synthesis. Origins Life 14 565-570. 

Shapiro, R. 1988. Prebiotic ribose synthesis. A critical analysis. Origins life Evol. Biosph. 18 71-85. 

Shapiro, R. 1999. Prebiotic cytosine synthesis A critical analysis. Implications for die origin of life. Proc. Natl. Acad. Sci. U.S.A. 96 4396-4401. 

The synthesis developed by Abramovitch and Shapiro (110) utilizes the formation of 6-methoxy-l-keto-l, 2,3,4-tetrahydro-/3-carboline (XII) by the Fischer cyclization of the p-methoxyphenylhydrazone (XI) of 2,3-dioxopiperidine. Alkaline hydrolysis of XII and decarboxylation of the product (XIII) gave 5-methoxytryptamine (HO), demethylation of which had previously been reported (103). 

J. J. Eisch, P. O. Otieno, K. Mackenzie, and B. W. Kotowicz, Electronic and Steric Design of Novel Group 13 Lewis Acids and Their Synthesis via Metal-Tin Exchange Reactions (1) Toward the Ideal Olefin Polymerization Catalyst, in Group 13 Chemistry From Fundamentals to Appheations , ACS Symposium Series 822, eds. P. J. Shapiro and D. A. Atwood, American Chemical Society, Washington, DC, 2002, p. 88. 

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