- Dolastatins 24. Synthesis of (-)-dolastatin 10. X-Ray molecular structure of N,N-dimethylvalyl-valyl-dolaisoleuine tert-butyl ester
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Total synthesis of the extraordinary antineoplastic constituent, dolastatin 10, from the Indian Ocean mollusc Dolabella auricularia has been summarized. The final synthetic step involved diethyl cyanophosphonate-mediated coupling of Dov-Val-Dil with Dap-Doe. Improved syntheses of these important precursors has led to a very practical synthesis of natural dolastatin 10. Important details of the HPLC and high-field (500 MHz) NMR characterization techniques employed to confirm the purity of dolastatin 10 have been recorded. Copyright 1996 by the Royal Society of Chemistry.
- Pettit, George R.,Srirangam, Jayaram K.,Singh, Sheo Bux,Williams, Michael D.,Herald, Delbert L.,Barkoczy, Jozsef,Kantoci, Darko,Hogan, Fiona
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- Efficient stereoselective synthesis of dolastatin 10, an antineoplastic peptide from a sea hare
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The stereoselective and efficient synthetic route to dolastatin 10, an antineoplastic peptide from a sea hare, has been developed. Dolaproine, one of the unusual constituents, was prepared in a highly stereoselective manner by the Evans aldol methodology.
- Hamada, Yasumasa,Hayashi, Kyoko,Shioiri, Takayuki
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- A practical approach to asymmetric synthesis of dolastatin 10
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Dolastatin 10, an antineoplastic agent for cancer chemotherapy, is a linear peptide possessing N,N-dimethyl Val-OH, l-valine, (3R,4S,5S)-dolaisoleucine, (2R,3R,4S)-dolaproine and (S)-dolaphenine. Our efficient synthesis includes the following three key features: (1) SmI2-induced cross-coupling was employed to couple aldehyde 11 with (S)-N-tert-butanesulfinyl imine 12 to generate the required stereocenters of Dap (7); (2) asymmetric addition of chiral N-sulfinyl imine 10 provided a straightforward approach to the synthesis of the protected Doe ((S,S)-8); (3) a practical method to the key subunit Val-Dil (24a) has been established as an alternative synthetic route for the synthesis of this challenging chemical structure.
- Zhou, Wen,Nie, Xiao-Di,Zhang, Yu,Si, Chang-Mei,Zhou, Zhu,Sun, Xun,Wei, Bang-Guo
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p. 6119 - 6131
(2017/08/02)
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- Total synthesis of dolastatin 10 through ruthenium-catalyzed asymmetric hydrogenations
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A total synthesis of dolastatin 10, a potent inhibitor of microtubule assembly, which displayed remarkable antineoplastic activity, is reported. Our synthetic approach was based upon ruthenium-promoted asymmetric hydrogenation of β-keto esters derived from (S)-Boc-proline and (S)-Boc-isoleucine for the construction of the two key units: (2R,3R)-Boc-dolaproine (Dap) and (3R)-Boc-dolaisoleucine (Dil).
- Mordant, Céline,Reymond, Sébastien,Tone, Hitoshi,Lavergne, Damien,Touati, Ridha,Ben Hassine, Bechir,Ratovelomanana-Vidal, Virginie,Genet, Jean-Pierre
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p. 6115 - 6123
(2008/02/04)
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- Synthesis and antitumor activity of novel dolastatin 10 analogs
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Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.
- Miyazaki,Kobayashi,Natsume,Gondo,Mikami,Sakakibara,Tsukagoshi
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p. 1706 - 1718
(2007/10/03)
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A stepwise synthesis of dolastatin 10 starting from the dolaphenine residue is described. The chiral dola isoleuine and dolaproine residues were obtained by 5-step procedures from the corresponding N-Boc amino acid. The key steps are respectively the NaBH4 reduction of an allylic ketone and the addition of an achiral Z-crotylboronate on the N-Boc-L-prolinal. Peptidic couplings were efficiently realised with reagents developed in the laboratory.
- Roux, Florence,Maugras, Isabelle,Poncet, Joel,Niel, Gilles,Jouin, Patrick
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p. 5345 - 5360
(2007/10/02)
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- Stereoselective Synthesis of Dolastatin 10 and Its Congeners
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Efficient synthesis of dolastatin 10 (1), a potent antitumor peptide from a sea hare Dolabella auricularia, has been achieved in a stereoselective manner.Trisnordolastatin 10 (2) and its C9-epimer (3) have also been synthesized.
- Shioiri, Takayuki,Hayashi, Kyoko,Hamada, Yasumasa
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p. 1913 - 1924
(2007/10/02)
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- An expeditious synthesis of dolastatin 10
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Total synthesis of dolastatin 10 (1) was completed by developing an efficient synthesis of two key amino acid components, Dil (6) and Dap (11), and subsequent stepwise coupling of five amino acid components from C-terminal Doe.
- Tomioka, Kiyoshi,Kanai, Motomu,Koga, Kenji
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p. 2395 - 2398
(2007/10/02)
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