Bio-inspired Step-Economical, Redox-Economical and Protecting-Group-Free Enantioselective Total Syntheses of (−)-Chaetominine and Analogues

Full details of the enantioselective four-step and five-step total syntheses of(−)-chaetominine from D-Trp and L-Trp are described.Featuring an oxidative double cyclization reaction,and tandem C14 epimerization-lactamization reactions as key steps,the method provides a rapid access to(−)-chaetominine(6a)and analogues.The total syntheses of(−)-chaetominine(6a)are so far the most concise and efficient.Through comprehensive investigation,the stereochemical requirements for the double cyclization reaction were revealed,and the confusion regarding physicochemical properties of this natural product was clarified.Moreover,short pathways to complexity generation,a scenarios revealed for the biosynthesis of fungal peptidyl alkaloid multi-cyclic scaffolds,have been validated through the chemical synthesis.On the basis of these findings,a plausible biosynthetic pathway for(−)-chaetominine(6a)was suggested.

Catalytic Asymmetric Total Synthesis of Macrocyclic Marine Natural Product(-)-Haliclonin A

of main observation and conclusion We describe the full details of our total synthesis of haliclonin A,a macrocyclic natural product suggested to originate from a common biosynthetic intermediate as sarain A.Central to our synthetic route is the strategic employment of nitromethane for several purposes:(1)as an umpolung surrogate of an aminomethyl group;(2)as an ideal nucleophile for the highly enantioselective catalytic asymmetric conjugate addition to forge the challenging all-carbon quaternary stereogenic center that was used to induce the formations of all other chiral centers of the molecule;and(3)as a CiNi building block to form the 3-azabicyclo[3.3.1]nonane framework.The realization of this strategy relied on the development of a novel organocatalytic asymmetric conjugate addition of nitromethane to 3-alkenyl cyclohex-2-enone;and the first Pd-promoted intramolecular coupling of a thiocarbamate moiety onto an electron-deficient alkene(enone)to form the 3-azabicyclo[3,3,l]nonane core.The synthesis also features a Sml2-mediated intermolecular reductive coupling of an enone with an aldehyde,ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocycles,and an unprecedented direct transformation of enol into enone.

An attempted approach to the tricyclic core of haliclonin A：Structural elucidation of the final product by 2D NMR

We describe the design and execution of a novel synthetic route to the tricyclic core of haliclonin A,a tetracyclic marine natural product.The approach features Bachi＇s thiol-medicated free radical cyclization of alkenyl isocyanide to build the bridged ring system,and ring-closing metathesis（RCM） reaction to form the macrocycle.Execution of the synthetic plan ultimately resulted in a diazatricyclic compound.By means of 2D NMR techniques,the structure of this compound was revealed to an unexpected product 8.Analysis of the synthetic pathways allowed concluding that the unexpected product is a result of an ＂unexpected＂ migration of olefinic bond during dioxolanation of the 2-cyclohexenone derivative 7.This investigation also resulted in a concise construction of the functionalized hexahydro-1H-isoindole-1,5（4H）-dione 12 and the macrocyclic tricyclic ring system 8.

Low-Valent Titanium-Mediated Enantioselective Synthesis of Quinazolinone Alkaloids Circumdatins F,H,and Analogs

We report the concise and protecting-group-free enantioselective total syntheses of circumdatins F and H.In view of the extreme importance of analogs of quinazolinone alkaloids in drug research and discovery,four analogs of bioactive quinazolinobenzodiazepine alkaloids,including demethoxycircumdatin H(12)and N-demethyl-benzomalvin A(13),have been synthesized.The method is based on the low-valent titanium-promoted intra-molecular reductive coupling of imides with o-nitrobenzimides,which yielded quinazolino[3,2-a][1,4]benzodi-azepines under mild conditions.In addition,heptacyclic dehydraasperlicin E(16)has been synthesized from asper-licin C by a NCS-mediated dehydra-cyclization reaction.