Total Synthesis of (+)‐Madangamine D

Ballette, Roberto; Pérez, Maria; Proto, Stefano; Amat, Mercedes; Bosch, Joan

doi:10.1002/ange.201402263

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…A RCM reaction of 25 was carried out with Grubbs 1 st generation catalyst in CH2Cl2, under high dilution conditions, at 40 ºC to close the D ring efficiently, giving tetracyclic enone 26 in 82% yield. 23 Subsequent treatment of 26 with palladium on carbon under a ~1 bar hydrogen atmosphere gave saturated ketone 3. Overreduction product S6 accounted for the rest of the material and could be converted back to ketone 3, employing catalytic AZADO and PIDA as the oxidant, in high yield.…”

Section: Resultsmentioning

confidence: 99%

“…[11][12][13][14][15][16][17][18][19][20][21][22] However, there exist only two reports of total syntheses of members of the family and a single formal synthesis of madangamine A (Figure 1B). [23][24][25][26] In 2014, Amat reported the first asymmetric total synthesis of madangamine D, employing a stereoselective cyclocondensation of phenylglycinol to establish an enantio-enriched bicyclic (rings BC) scaffold. In 2017, Chida and Sato's unified total synthesis of madangamine's A, C and E demonstrated the divergent application of a late-stage tetracyclic intermediate.…”

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confidence: 99%

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A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E

Shiomi

Shennan

Yamazaki

et al. 2021

Preprint

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The enantioselective total synthesis of madangamine E has been completed in 30 steps, enabled by a new catalytic and highly enantioselective desymmetrizing intramolecular Michael addition reaction of a prochiral ketone to a tethered β,β’-disubstituted nitroolefin. This key carbon–carbon bond forming reaction efficiently constructed a chiral bicyclic core in near-perfect enantio- and diastereo-selectivity, concurrently established three stereogenic centers, including a quaternary carbon stereocenter, and proved highly scalable. Furthermore, the pathway and origins of enantioselectivity in this catalytic cyclisation were probed using density functional theory (DFT) calculations, which revealed the crucial substrate/catalyst interactions in the enantio-determining step. Following construction of the bicyclic core, the total synthesis of madangamine E could be completed, with key steps including a mild one-pot oxidation-lactamisation, a two-step Z-selective olefination of a sterically hindered ketone, and ring-closing metatheses to install the two macrocyclic rings.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E

Shiomi

Shennan

Yamazaki

et al. 2021

Preprint

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“…An anti-addition of cuprate to the α,β-unsaturated γmethyllactam was essential to accomplish the synthesis of (±)-subincanadine C. However, the recent literature precedents, including one from our research group, state that exclusive syn-addition of cuprate takes place on such type of substrates and the scientific reason for such unusual stereoselections is still unknown. 13,24,25 As depicted in Scheme 4, we planned to study the feasibility of anti-addition of cuprate to indolizinoindolone 15 to accomplish the synthesis of (±)-subincanadine C. Imide 1 on selective 1,2-addition of methylmagnesium iodide followed by acid-induced Pictet− Spengler cyclization furnished the desired indolizinoindolone 15 in 85% yield over two steps. The planned 1,4-addition of allyl cuprate to compound 15 also exclusively yielded an unusual syn-addition product 16 in 83% yield.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Diastereoselective Synthesis of (±)-epi-Subincanadine C

Kalshetti

Argade

2018

ACS Omega

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Starting from indolylmaleimide, concise and efficient total synthesis of (±)- epi -subincanadine C was described via stereoselective Wittig olefination, base-induced selective mono-prenylation, regioselective Grignard reaction, diastereoselective Pictet–Spengler cyclization, regioselective oxidative carbon–carbon double-bond cleavage, one-pot reductions, and intramolecular cyclization pathway. An attempted synthesis of (±)-subincanadine C via diastereoselective Grignard addition to the α,β-unsaturated γ-lactam or diastereoselective reduction of a carbon–carbon double bond also resulted in yet another route to (±)- epi -subincanadine C.

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“…[10] A recent approach contributed by the Douglas group featured Pd-catalysed C-C bond activation and cyanoamidation cascades. [15] Nevertheless, only three groups completed the total syntheses of selected madangamine alkaloids, including the Bosch and Amat, [16][17][18] Sato and Chida [8,19] and Dixon [20] groups.…”

Section: Chemical Synthesis: State Of the Artmentioning

confidence: 99%

“…The Bosch-Amat group reported the total synthesis of (þ)-madangamine D in 2014 as the first member ever synthesized. [16] The ring-forming sequence in Bosch-Amat's pioneering work featured a rapid construction of the diazatricyclic core, a successful ring closing metathesis (RCM) reaction to build the D-ring, and furnishing the E-ring via macrolactamization.…”

Section: Bosch-amat's Approach Towards Madangamines D and A (2014 And...mentioning

confidence: 99%