Yu-Ming Zhao

Formal Synthesis of (−)‐Cephalotaxine Based on a Tandem Hydroamination/Semipinacol Rearrangement Reaction

( )-Cephalotaxine 1 was first isolated from Cephalotaxus drupacea and C. fortunei as a major alkaloid among a series of its ester derivatives in 1963. Much attention has been paid towards the studies of cephalotaxine due to the unique pentacyclic structure and antileukemic activity of its derivatives. As a classic target for organic chemists, the syntheses of cephalotaxine have been continuing since the pioneering work of Weinreb and Semmelheck in 1972. Among the various strategies reported, the establishment of the 1azaspiroACHTUNGTRENNUNG[4.4]nonane ring system 2 followed by benzazepine formation were most frequently introduced (Figure 1). Thus, an effective construction of this unit would be of great importance in the synthesis of cephalotaxine and other structurally related alkaloids such as serratine and stemonamine. Azaspiro ACHTUNGTRENNUNG[4.4]nonane 2-type azaspirocycles have long been recognized as useful building blocks and recently been selected as templates for pharmaceutical investigations. A number of methods have been developed to construct this structural unit in the context of total synthesis. However, these methods often require multiple manipulations, installing the aza-quaternary carbon center and each of the spiro rings in separate steps. Additionally, chiral syntheses of this unit are mainly based either on chiral auxiliaries or chiral starting materials. As far as we are aware, catalytic asymmetric synthesis of this kind of azaspirocycles has not been reported. In connection with our longstanding works on the semipinacol rearrangement reaction and its application in total synthesis of polycyclic alkaloids, we intended to develop a highly efficient catalytic asymmetric formal synthesis of ( )-1, taking advantage of the tandem hydroamination/semipinacol rearrangement reaction. As shown in Scheme 1, according to the procedure by Isono and Mori, ( )-cephalotaxine 1 could be obtained in four steps from 3, which has generally been introduced as

An Efficient Total Synthesis of (±)-Stemonamine

An efficient first approach to the Stemona alkaloid (+/-)-Stemonamine has been developed on the basis of a key TiCl4 promoted tandem Semipinacol rearrangement/Schmidt reaction and a Dieckmann condensation reaction.

Formal syntheses of (+/-)-stemonamine and (+/-)-cephalotaxine.

A short and efficient approach to aza-quaternary pyrrolo[1,2-a]azepine 8 and aza-quaternary indolizine 23, as the crucial intermediates for syntheses of stemonamine (1a) and cephalotaxine (1b), has been developed on the basis of the key intramolecular Schmidt reaction of symmetric azido-diones 5 and 18, respectively.

One-Step Construction of Tetrahydro-5H-indolo[3,2-c]quinolines from Benzyl Azides and Indoles via a Cascade Reaction Sequence

A novel one-step assembly of tetrahydro-5H-indolo[3,2-c]quinolines from benzyl azides and indoles via a formal [4 + 2] cycloaddition is described. A cascade reaction sequence, which involves benzyl azide-to-iminium rearrangement followed by two sequential Pictet-Spengler reactions, generates the tetracycles in moderate to excellent yields. The current method is applicable to a broad substrate scope and holds significant potential in constructing polycyclic indolines with tertiary and/or quaternary carbon centers.

One-Pot Synthesis of Aminoenone via Direct Reaction of the Chloroalkyl Enone with NaN3: Rapid Access to Polycyclic Alkaloids

A new one-pot procedure for the preparation of aminoenone from chloroalkyl enone and sodium azide was demonstrated. The structure of the presumed triazoline intermediate in this process was confirmed by X-ray analysis for the first time. As the application of this methodology, the synthesis of polycyclic alkaloid hexahydroapoerysopine (1a) was achieved through an efficient synthetic route.

CCDC 804165: Experimental Crystal Structure Determination

Related Article: Ming Yang, Yu-Ming Zhao, Shu-Yu Zhang, Yong-Qiang Tu, Fu-Min Zhang|2011|Chem.Asian J.|6|1344|doi:10.1002/asia.201100171