Divergent Total Synthesis of Triptolide, Triptonide, Tripdiolide, 16-Hydroxytriptolide, and Their Analogues

A divergent route was developed for the formal total synthesis of triptolide, triptonide, and tripdiolide, as well as a total synthesis of 16-hydroxytriptolide and their analogues in an enantioselective form. Common advanced intermediate <b>5</b> was concisely assembled by employing an indium­(III)-catalyzed cationic polycyclization reaction and a palladium-catalyzed carbonylation–lactone formation reaction as key steps. This advanced intermediate was readily converted to the above natural products by using palladium-catalyzed cross-coupling or the Claisen rearrangement reaction as key steps. Additionally, preliminary structure–cytotoxic activity relationship studies of C13 suggested that it might be a new modification site that could still retain the cytotoxicity

Divergent Total Synthesis of Triptolide, Triptonide, Tripdiolide, 16-Hydroxytriptolide, and Their Analogues

A divergent route was developed for the formal total synthesis of triptolide, triptonide, and tripdiolide, as well as a total synthesis of 16-hydroxytriptolide and their analogues in an enantioselective form. Common advanced intermediate 5 was concisely assembled by employing an indium­(III)-catalyzed cationic polycyclization reaction and a palladium-catalyzed carbonylation–lactone formation reaction as key steps. This advanced intermediate was readily converted to the above natural products by using palladium-catalyzed cross-coupling or the Claisen rearrangement reaction as key steps. Additionally, preliminary structure–cytotoxic activity relationship studies of C13 suggested that it might be a new modification site that could still retain the cytotoxicity

Divergent Total Synthesis of Triptolide, Triptonide, Tripdiolide, 16-Hydroxytriptolide, and Their Analogues

A divergent route was developed for the formal total synthesis of triptolide, triptonide, and tripdiolide, as well as a total synthesis of 16-hydroxytriptolide and their analogues in an enantioselective form. Common advanced intermediate <b>5</b> was concisely assembled by employing an indium­(III)-catalyzed cationic polycyclization reaction and a palladium-catalyzed carbonylation–lactone formation reaction as key steps. This advanced intermediate was readily converted to the above natural products by using palladium-catalyzed cross-coupling or the Claisen rearrangement reaction as key steps. Additionally, preliminary structure–cytotoxic activity relationship studies of C13 suggested that it might be a new modification site that could still retain the cytotoxicity

Rh(III)-Catalyzed Intramolecular Redox-Neutral or Oxidative Cyclization of Alkynes: Short, Efficient Synthesis of 3,4-Fused Indole Skeletons

A Rh­(III)-catalyzed intramolecular redox-neutral or oxidative annulation of a tethered alkyne has been developed to efficiently construct 3,4-fused indoles via a C–H activation pathway. The advantages of this process are (1) ready availability of annulation precursors; (2) broad substrate scope; (3) complete regioselectivity; (4) simple and mild reaction conditions; and (5) no need for an external oxidant or to employ molecular oxygen as the stoichiometric terminal oxidant

Access to Six- and Seven-Membered 1,7-Fused Indolines via Rh(III)-Catalyzed Redox-Neutral C7-Selective C–H Functionalization of Indolines with Alkynes and Alkenes

We report herein a new strategy for the Rh­(III)-catalyzed redox-neutral C7-selective C–H activation/annulation of indolines to rapidly access various privileged 1,7-fused indolines by utilizing an oxidizing–directing group. For example, a Rh­(III)-catalyzed redox-neutral C7-selective C–H functionalization of indolines with arylalkynes is described to directly access 7-membered 1,7-fused indolines. Moreover, an unprecedented intramolecular addition of an alkenyl-Cp*Rh­(III) species to a carbamoyl moiety occurred to give 1<i>H</i>-pyrroloquinolinones when employing alkyl alkynes. Additionally, an efficient Rh­(III)-catalyzed redox-neutral C7-selective C–H activation/alkenylation/aza-Michael addition of indolines is also developed to give 6-membered 1,7-fused indolines. The advantages of these processes are as follows: (1) mild and simple reaction conditions; (2) no need for an external oxidant; (3) broad scope of substrates; and (4) valuable six- or seven-membered 1,7-fused indolines as products

<i>Streptococcus suis</i> synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5ʹ-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions in vitro and it is an important virulence factor. Here, we show that S. suis 5ʹ-nucleotidase not only enables producing 2ʹ-deoxyadenosine from 2ʹ-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2ʹ-deoxyadenosine and adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis indicated that the production of 2ʹ-deoxyadenosine by 5ʹ-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The in vivo infection experiment showed that 2ʹ-deoxyadenosine synthesized by 5ʹ-nucleotidase caused monocytopenia in mouse blood. The in vivo transcriptome analysis in mouse blood showed the inhibitory effect of 5ʹ-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that S. suis synthesizes 2ʹ-deoxyadenosine and adenosine by 5ʹ-nucleotidase to dampen host immune responses, which represents a new mechanism of S. suis pathogenesis.</p