Synthesis and absolute configuration of Tanret's (‐)‐pelletierine

Abstract

The synthesis is described of (-)-pelletierine picrate identical with Tanref's pelletierine picrate from Punica granaturn L. and of its antipode by oxidation, respectively, of (-)-and of (+)-sedridine. The sedridines are alkaloids with known absolute configuration of the piperidine asymmetric carbon atom. From this follows the Ds-configuration of (-)-pelletierine. 1. From the bark of the pomegranate tree (Punica granatum L.) CharlesTanret isolated four alkaloids, which he named pelletierine, methylpelletierine, isopelletierine, and pseudopelletierine 2, 3 . The structure of pseudopelletierine was the first to be elucidated 4. Tanret's methylpelletierine proved to be N-methylisopelletierine 4. Isopelletierine was soon inferred to have structure I, 1-(2-piperidyl)-propan-2-0ne 4 ; this was confirmed by certain syntheses 5 , 6 . Pelletierine, the fourth alkaloid of the group, presented an intriguing structural problem 7, which is summarized below. Ch. Tanref had described pelletierine as an optically active liquid-base isomeric with an optically inactive base, which he therefore named isopelletierine and regarded as being probably the racemate of pelletierine. Tanret, in 1880, recorded the rotation of the sulphate, [a]D -30" 3. This report was discounted, however, when K. Hess in 1917 in a reinvestigation of the isolation confirmed the optical inactivity of isopelletierine, but A preliminary account has been given by H. C.

Strategies for the Asymmetric Construction of Pelletierine and its Use in the Synthesis of Sedridine, Myrtine, and Lasubine

“…Following a two recent reports, the enantioselective version of this type of IMAMR was also studied as a means to produce enantioenriched 17 . [7o], [7p] Thus, under Sánchez‐Roselló's and Fan's conditions, treatment of 23 with quinine‐based amine 24a gave (+)‐ 17 in good yield (Scheme ). Importantly the pseudo ‐enantiomer of 24a is commercially available, therefore, the enantiomeric form of 17 was similarly accessed from quinidine‐based amine 24b in similar yield.…”

“…Based on a reported procedure the synthesis of racemic pelletierine 6 was achieved as shown in Scheme . [7c] Piperidine 13 was initially N‐ halogenated and the intermediate N ‐chloro compound was then immediately dehydrohalogenated. As reported, the product from this process is a mixture of compounds which represent surrogates for imine 14 .…”

“…An asymmetric organocatalytic version of the intermolecular Mannich reaction detailed in Scheme has been reported by Bella. [7n] We have used this method to prepare both optically active versions of pelletierine and in turn used this material to prepare analogues of febrifugine ( 12 ) . As summarized in Scheme , use of l ‐ or d ‐proline facilitated the enantioselective intermolecular Mannich reaction of 14 with an excess of acetone in a DMSO‐water (9:1) solvent mixture.…”

“…(–)‐(2 S )‐(2‐Oxopropyl)piperidine‐1‐carbamic acid benzyl ester (Cbz‐pelletierine) 17: [7n] Δ 1 ‐Piperideine 14 (670 mg, 8.06 mmol, 1 eq. ), acetone (27 mL, 367.59 mmol, 46 eq.…”

“…Compound 6 has an interesting history: it is isolated in an optically active form, however, it co‐occurs with a compound termed isopelletierine, which is simply racemic pelletierine (it is now appreciated that β‐keto amines, like 6 , undergo isomerisation, see Scheme ) and its exact structure was not unequivocally confirmed until its first synthesis in 1961 . More recently several new methodologies have been developed to obtain this and related molecules in optically active form . Part of this interest stems from the fact that 6 represents a useful, functionalized building block to assemble more complex structures .…”