Total Synthesis of (+)‐Dibromophakellin and (+)‐Dibromophakellstatin

Imaoka, Takuya; Akimoto, Takafumi; Iwamoto, Osamu; Nagasawa, Kazuo

doi:10.1002/asia.201000213

Cited by 30 publications

(16 citation statements)

References 251 publications

(224 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At this stage, the structure of the synthetic intermediate including the trans -bicyclo[3.3.0]octane skeleton was unambiguously confirmed by an X-ray diffraction study ( Supplementary Method and Supplementary Data 1 ). Treatment of 21 with LHMDS and methanesulfonyl chloride at −78 to −40 °C induced a sequential reaction of mesylation, the elimination of mesylate and the addition of nitrogen to the isothiourea moiety to give pentacyclic 22 in 65% yield, in a manner similar to that of the synthesis of (+)-dibromophakellstatin reported by Nagasawa and colleagues 51 . Having constructed a C-ring, we next tried to form an F-ring.…”

Section: Resultssupporting

confidence: 59%

Total synthesis of palau’amine

et al. 2015

View full text Add to dashboard Cite

Palau'amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau'amine characterized by the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N–N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation) and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The synthetic palau'amine is confirmed to exhibit excellent immunosuppressive activity. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity.

show abstract

Section: Resultssupporting

confidence: 59%

Total synthesis of palau’amine

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The total synthesis of (±) –dibromophakellin has been completed, 7,8,9 as well as the enantioselective synthesis of (+)-dibromophakellin. 10,11 In addition to the phakellins, (−)-dibromophakellstatin ( 3 ) also resembles, in part, the palau’amine core structure. (−)-Dibromophakellstatin ( 3 ) was first isolated in 1997 by Pettit, 12 and its total synthesis has been completed by Lindel’s group.…”

mentioning

confidence: 99%

Palau’amine and Related Oroidin Alkaloids Dibromophakellin and Dibromophakellstatin Inhibit the Human 20S Proteasome

et al. 2012

View full text Add to dashboard Cite

We report herein that the oroidin-derived alkaloids, palau’amine (1), dibromophakellin (2) and dibromophakellstatin (3) inhibit the proteolytic activity of the human 20S proteasome as well as the i20S immunoproteasome catalytic core. Palau’amine is found to prevent the degradation of ubiquitinylated proteins, including IκBα, in cell culture, which may be indicative of the potential mechanism by which these agents exhibit their exciting cytotoxic and immunosuppressive properties.

show abstract

“…Treatment of 27 with LHMDS and methanesulfonyl chloride (MsCl) at 78 to 40 induced the sequential reactions of mesylation, elimination of mesylate, and addition of the isothiourea to give pentacycle 28 in 65% yield in a manner similar to that seen in the synthesis of ( ) dibromophakellstatin reported by Nagasawa. 15 Having constructed the C ring, we next tried to form the F ring. Only reductive conditions using diisobutylaluminium hydride (DIBAL) were successful for the removal of the tri uoroacetyl group, and subsequent treatment of the resulting amine with CbzNCS afforded thiourea 29 in good yield.…”

Section: Total Synthesis Of Palau Aminementioning

confidence: 99%

Total Synthesis of Palau’amine

Namba

Takeuchi²,

Kaihara³

et al. 2017

J. Synth. Org. Chem. Jpn.

View full text Add to dashboard Cite

Palau amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and signi cant immunosuppressive activity. Here, we report the total synthesis of palau amine characterized by the Hg(OTf) 2 catalyzed construction of tetra substituted carbon center at the C16 position and the construction of an ABDE tetracyclic ring core including a trans bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D ring formation), and the condensation of pyrrole with methyl ester (B ring formation) in a single step. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity.

show abstract

Total Synthesis of (+)‐Dibromophakellin and (+)‐Dibromophakellstatin

Abstract: A new method for the preparation of quaternary chiral aminals has been developed that employs an enamide-type Overman rearrangement process. This methodology was applied to enantioselective total syntheses of (+)-dibromophakellin and (+)-dibromophakellstatin.

Cited by 30 publications

References 251 publications

Total synthesis of palau’amine

Total synthesis of palau’amine

Palau’amine and Related Oroidin Alkaloids Dibromophakellin and Dibromophakellstatin Inhibit the Human 20S Proteasome

Total Synthesis of Palau’amine

Contact Info

Product

Resources

About