Unified Total Syntheses of (−)‐Medicarpin, (−)‐Sophoracarpan A,and (±)‐Kushecarpin A with Some Structural Revisions

The total syntheses of medicarpin, sophoracarpan A, and kushecarpin A from a common intermediate are achieved by using ortho‐ and para‐quinone methide chemistry. Additionally, the relative stereochemistry of sophoracarpan A and B have been reassigned.     

A General Entry to Antifeedant Sesterterpenoids: Total Synthesis of (+)‐Norleucosceptroid A, (−)‐Norleucosceptroid B,and (−)‐Leucosceptroid K

The first asymmetric total synthesis of the antifeedant terpenoids (+)‐norleucosceptroid A, (−)‐norleucosceptroid B, and (−)‐leucosceptroid K has been accomplished. This highly concise synthetic route was guided by our efforts to develop a platform for the collective synthesis of a whole family of antifeedant natural products. The synthesis features a Hauser–Kraus‐type annulation followed by an unprecedented, highly efficient intramolecular dilactol aldol‐type condensation reaction to produce the 5,6,5 skeleton. The developed synthetic route proceeds for norleucosceptroid A and B in 16 steps (longest linear sequence) from known compounds.     

Unified Asymmetric Total Syntheses of (−)‐Alotaketals A–D and (−)‐Phorbaketal A

The novel tricyclic spiroketal alotane‐type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (−)‐alotaketals A–D and (−)‐phorbaketal A were accomplished [29–31 steps from (−)‐malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ‐keto‐alcohols to forge the common tricyclic spiroketal intermediate, 2) a late‐stage allylic C−H oxidation, and 3) olefin cross‐metathesis to install the different side chains.     

Total Synthesis of (−)‐Salvinorin A

Salvinorin A ( 1 ) is natural hallucinogen that binds the human κ‐opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l ‐(+)‐tartaric acid into that of (?)‐ 1 via an unprecedented allylic dithiane intramolecular Diels–Alder reaction to obtain the trans‐decalin scaffold. Tsuji allylation set the C9 quaternary center and a late‐stage stereoselective chiral ligand‐assisted addition of a 3‐titanium furan upon a C12 aldehyde/C17 methyl ester established the furanyl lactone moiety. The tartrate diol was finally converted into the C1,C2 keto‐acetate.     

Enantioselective Total Syntheses of (−)‐Rhazinilam, (−)‐Leucomidine B,and (+)‐Leuconodine F

A divergent total synthesis of three structurally distinct natural products from imine 9 was accomplished through an approach featuring: 1) a Pd‐catalyzed decarboxylative cross‐coupling, and 2) heteroannulation of 9 with bromoacetaldehyde and oxalyl chloride to give tetrahydroindolizine 6 and dioxopyrrole 7 , respectively. The former was converted into (−)‐rhazinilam, while the latter was converted into (−)‐leucomidine B and (+)‐leuconodine F. A substrate‐directed highly diastereoselective reduction of a sterically unbiased double bond by using a homogeneous palladium catalyst was developed. A self‐induced diastereomeric anisochronism (SIDA) phenomenon was observed for leucomidine B.