Pyruvic Acid Dimethylhydrazone. A Synthetic Equivalent of the Pyruvic Acid Dianion

Abstract

The pyruvic acid dimethyl hydrazone can be easily prepared in ether. This compound, after deprotonation with alkyllithium, forms a strong nucleophile which on treatment with electrophiles and acidic work up yield α-ketoacids, α-hydroxybutenolides or α,γ-diketoacids.

1-Azaallylic Anions in Heterocyclic Chemistry

“…Using the previous ω-haloimine chemistry, the synthesis of stenusine (209), the spreading agent of the staphynilid beetle Stenus comma, was accomplished. 85 First, alkylation of N-tert-butylaldimine 203 via its 1-azaallylic anion with 1-bromo-2-methylbutane (204), followed by separation from some dialkylated product, and second alkylation with 1-bromo-3-chloropropane (198) resulted in the corresponding δ-chloroaldimine 206 (Scheme 41). After hydrolysis and conversion to the corresponding Nethylaldimine 208, cyclization to 209 was accomplished with lithium aluminum hydride, giving a 1:1 mixture of two diastereoisomers.…”

“…Two equivalents of methyllithium was needed to generate the strongly ambident anion 646, which condensed with a series of aldehydes and ketones to form γ,γ-disubstituted 2-hydroxybutenolides 648 upon acid workup (Scheme 129). 198 The same synthetic strategy could be extended to N-sulfonylhydrazones derived from acetone. Treatment of N-sulfonylhydrazone 649 with 2 equiv of n-butyllithium at -70 °C gave the dianion 650, which, under Shapiro conditions, led to the formation of trianion 651.…”

The identification and optimization of 2,4-diketobutyric acids as flap endonuclease 1 inhibitors

“…21 The dimethyl hydrazone of pyruvic acid was used as the nucleophile (Scheme 1, Method B). The hydrazone was easily prepared on a 60 mmol scale and was stable for at least 1 month at 0°C.…”

“…23 In general, unsubstituted heterocycles showed poor activity (19,25). 5-Substituted furans were generally more potent but were quite selective for XPG (21)(22)(23)(24). 5-Substituted thiophenes were quite potent against FEN1, but showed little of the desired selectivity (26-29).…”

Synthesis of α‐Ketobutyrolactones and γ‐Hydroxy‐α‐Keto Acids.

“…There are several methods known for the synthesis of γ-hydroxy-α-keto acids. Key methods used are: (1) direct aldol condensation of pyruvic acid esters with aldehydes, 2 (2) reaction of anions derived from pyruvic acid dimethyl hydrazone, 3 (3) Lewis acid-promoted reaction of enol trimethylsilyl ethers of pyruvate esters with acetals, 4 (4) use of 3-bromopropyne for the introduction of the pyruvate moiety, 5 (5) use of thiazoles as a synthetic equivalent of a formyl group, 6 and (6) allylation of aldehydes using 2-(bromomethyl)acrylic acid. 7,8 We needed to secure a variety of γ-hydroxy-α-keto acids for evaluating specificity for new aldolase enzymes.…”