ChemInform Abstract: TOTALSYNTH. VON (+‐)‐CEPHARAMIN

Abstract

Durch Behandlung von 2′‐Brom‐reticulin (I) mit überschüssigem Trifluoressigsäureanhydrid bei 160°C wird in 7 l%iger Ausbeute das Stilben (II) erhalten, das sich in quantitativer Ausbeute mit Wasserstoff an PtO2 ′zum Dihydrostilben (III) hydrieren läßt. Bestrahlung der Verbindung (III) mit UV‐Licht in Gegenwart von Natronlauge und Natriumjodid führt zum Secomorphinandienon (IV), das sich durch Hydrolyse und intramolekulare Michael‐Addition in das Enon (V) umwandeln läßt (2% Ausbeute).

Substrate-Modified Functional Group Reactivity: Hasubanan and Acutumine Alkaloid Syntheses

“…At this juncture, two different alkyne addition reactions were investigated. Semihydrogenation of 33 with Crabtree's catalyst provided the cisalkene 34 (86%), which is a potential precursor to (−)-dechloroacutumine (48). Alternatively, hydrostannylation of 33 formed the vinylstannane 35 (67%).…”

“…Parallel threestep sequences comprising formate cleavage, oxidation of the newly formed alcohol, and site-and stereoselective reduction converted the formates 42 and 45 to the final precursors 43 and 46, respectively. Hetereogeneous hydrogenation of 43 and 46 (palladium on carbon) provided (−)-dechloroacutumine (48) in 36% and 60% yield, respectively. 86,87 Homogeneous hydrogenation of dehydroacutumine ( 46) ([Rh(nbd)(dppb)]-BF 4 , 300 psi H 2 ) furnished (−)-acutumine (47, 17% yield of 47 at 30% conversion of 46).…”

“…Acid-mediated deprotection of the cyclization product 36 afforded the diol 38 (71%). Our efforts turned toward elaboration of the cyclopentene of the diol 38 to the cyclopentenone of (−)-dechloroacutumine (48). This synthetic transformation required installation of the C-10 oxygen functionality of (−)-dechloroacutumine (48).…”

“…Our efforts turned toward elaboration of the cyclopentene of the diol 38 to the cyclopentenone of (−)-dechloroacutumine (48). This synthetic transformation required installation of the C-10 oxygen functionality of (−)-dechloroacutumine (48). Our initial approach to install the C-10 ketone involved selective oxidation of the diol 38 (manganese oxide) to the enone 72 (40%, Scheme 9).…”

Memory of Chirality in Bromoalkyne Carbocyclization: Applications in Asymmetric Total Synthesis of Hasubanan Alkaloids

“…The primary synthetic challenge posed by these alkaloids is the construction of the tetracyclic framework having an α-tertiary amine moiety. Since hasubanonine ( 1 ) and its related metabolites were first synthesized in racemic form in the 1970s, numerous total and formal syntheses of hasubanan alkaloids have been reported. , The first enantioselective total synthesis of a hasubanan alkaloid, (+)-cepharamine ( 3 ), was achieved in 1998 by the Schultz group utilizing the Birch alkylation of a chiral benzamide . In 2011, the Herzon group developed the efficient asymmetric entry to several hasubanan alkaloids including 1 and 2 , employing a Corey’s CBS-catalyzed enantioselective Diels–Alder reaction .…”