Asymmetric synthesis of (+)- and (−)-deoxyfebrifugine and deoxyhalofuginone

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

“…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. Both ( R )‐ and ( S )‐ 17 accessed from this study were used to prepare (–)‐ and (+)‐deoxyhalofuginone 26 , a compound of interest as an analogue of the natural product febrifugine ( 12 , Figure ) . The enantioexcess recorded for Cbz‐protected ( R )‐ and ( S )‐deoxyhalofuginone ( 25 ), derived from these sequences were 98 % and 90 % respectively and this high level of optical purity enabled an X‐ray crystal structure of ( R )‐ 25 to be obtained, which confirmed the sense of selectivity for the stereoselective IMAMR (Figure ).…”

“…This method was used to determine how many recrystallisation′s were required in order to ultimately obtain high optical purity of 17 (see ESI section). In terms of absolute stereochemistry, material obtained from either salt 28a and 28b was compared to the literature data and was also consistent with the previous work discussed above in Scheme and Scheme . In addition, the absolute stereochemistry of the insoluble salt 28a was further confirmed by single‐crystal X‐ray crystallography (Figure )…”

“…Reagents and conditions: (i) 24a (20 mol-%), TFA (40 mol-%), THF, r.t., 18 h, 91 %, 98 % ee; (ii) 24b (20 mol-%), TFA (40 mol-%), THF, r.t., 18 h, 90 %, 90 % ee; (iii) see ref. [15] ; (iv) HBr, AcOH, see ref. [15] .…”

Total Synthesis of 2‐(2‐Ketoalkyl)‐piperidine Alkaloids (+)‐ Pelletierine, (+)‐Haloxynine and (‐)‐N‐Methyl‐pelletierine via Regioselective Wacker Oxidation

“…Also the keto compounds 9e and 9f were obtained in satisfactory yields. We then attempted the synthesis of antimalarial quinazoline alkaloid analogue, (+)‐deoxyfebrifugine 8a via the Wacker oxidation of the corresponding olefinic compound 10g but we couldn't get the expected keto compound (Cbz‐protected deoxyfebrifugine) as the reaction mass turned into a complex mixture.…”

“…Therefore, asymmetric synthesis of 2‐substituted piperidine alkaloids has been the target of many laboratories. Various strategies employed for the synthesis include chiral pool, readily available chiral nitrogen compounds, organocatalytic aminoxylation, aza‐Michael reaction, aza‐Henry reaction, aza‐Diels‐Alder, chiral auxiliary approach, transition metal catalyzed reactions, Mannich reaction and chiral bases . From our laboratory, we have reported a few chiral syntheses of pyrrolidine and piperidine alkaloids .…”