Polyhydroxylated pyrrolizidines. Part I: Short and highly stereocontrolled syntheses of hyacinthacines

Chemoenzymatic Synthesis and Inhibitory Activities of Hyacinthacines A1 and A2 Stereoisomers

“…syn/anti mer of 7-deoxyalexine [7] ) and 2-epihyacinthacine A 2 (9) was confirmed by NMR analysis (see Supporting Information).…”

“…[2] The chemical syntheses of these compounds usually involve cumbersome protectiondeprotection reactions, elaborated starting materials derived from the sugar chiral pool, and therefore, moderate stereoselection and global yields are achieved. [7][8][9] Importantly, the generation of configurational diversity on the stereogenic centers appears to be of paramount importance to optimize their activity and selectivity. [10] Consequently, novel methodologies for the preparation of these compounds with a broad configurational diversity are of increasing interest.…”

A New Synthetic Approach to (+)‐Hyacinthacine A1 and the First Total Synthesis and Absolute Configuration Assignment of Naturally Occurring (+)‐Hyacinthacine A6

“…According to the above retrosynthetic analysis and based on the results from previous studies, [15] we began the synthesis (see Scheme 1) with (2R,3S,4R,5R)-3,4-bis(benzyloxy)-2Ј-O-(tert-butyldiphenylsilyl)-2,5-bis(hydroxymethyl)-pyrrolidine (3) which was chemoselectively transformed into its N-Boc derivative 4 by treatment with di-tert-butyl dicarbonate in dichloromethane (DCM)/triethylamine (TEA). Conventional benzoylation of 4 to the corresponding 5-(benzoyloxymethyl) derivative 5 followed by O-desilylation afforded the pyrrolidine 6, opportunely leaving the primary alcohol free for oxidation to aldehyde 7 (IR evidence: ν = 1725 cm -1 and no hydroxy absorption band) by N-methylmorpholine N-oxide (NMO) catalyzed by tetran-propylammonium perruthenate (TPAP) in preparation for Wittig-chain lengthening.…”

“…In this context in recent years our group has developed a synthetic methodology involving the use of appropriately functionalized and protected pyrrolidines [14] as key intermediates for the preparation of more complex polyhydroxylated pyrrolizidine alkaloids (PHPAs). [15] On the other hand, such polyhydroxylated pyrrolidines have been prepared from the commercially available hexulose, -fructose. Herein, we describe our studies on (+)-hyacinthacine A 1 (1) and (+)-hyacinthacine A 6 (2) which culminated in the second reported total enantioselective synthesis of 1 [16] and the first total synthesis and absolute configuration assignment of 2.…”

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

“…[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136] Nevertheless, the strategy also proved to be fruitful in the synthesis of xenovenine and some natural analogues isolated from tropical frogs, [137][138][139][140][141] isoretronecanol, 142 chysine B, 142 austra-line, 143,144 7-epi-alexine, 143 and 7a-epi-7-deoxycasuarine. 145 In few intriguing cases, acetals and ketals instead of the aldehydes or ketones have been employed in a similar fashion.…”