WO2021207511A1 - Meayamycin analogues and methods of use - Google Patents

Meayamycin analogues and methods of use Download PDF

Info

Publication number
WO2021207511A1
WO2021207511A1 PCT/US2021/026408 US2021026408W WO2021207511A1 WO 2021207511 A1 WO2021207511 A1 WO 2021207511A1 US 2021026408 W US2021026408 W US 2021026408W WO 2021207511 A1 WO2021207511 A1 WO 2021207511A1
Authority
WO
WIPO (PCT)
Prior art keywords
mmol
equiv
nmr
mhz
etoac
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2021/026408
Other languages
English (en)
French (fr)
Inventor
Dale L. BOBER
Naidu S. Chowdari
Sanjeev Gangwar
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bristol Myers Squibb Co
Scripps Research Institute
Original Assignee
Bristol Myers Squibb Co
Scripps Research Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bristol Myers Squibb Co, Scripps Research Institute filed Critical Bristol Myers Squibb Co
Priority to US17/916,947 priority Critical patent/US20230159552A1/en
Priority to KR1020227038786A priority patent/KR20220166828A/ko
Priority to CN202180027149.7A priority patent/CN115698018A/zh
Priority to JP2022561608A priority patent/JP2023521135A/ja
Priority to EP21722684.4A priority patent/EP4132934A1/en
Publication of WO2021207511A1 publication Critical patent/WO2021207511A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • This disclosure relates to meayamycin and analogues thereof having cytotoxic activity, methods for their preparation, and methods of using them, particularly as anti-cancer agents.
  • FR901464 originally isolated from the bacteria Pseudomonas sp. No. 2663 (Ref. 1), is the first member of a growing class of potent antitumor antibiotics that now includes the spliceostatins (Ref. 2) and thailanstatins (Ref. 3).
  • Total syntheses of FR901464 confirmed the assigned structure and relative stereochemistry within each noncontiguous subunit and permitted assignment of its absolute stereochemistry (Refs. 4-8).
  • This disclosure relates to the synthesis of meayamycin and novel analogues thereof, especially modifications centered on left-hand subunit, and includes a short, scalable total synthesis of meayamycin proper.
  • this disclosure provides a compound according to formula (I): wherein R is
  • a method of treating a subject suffering cancer comprising administering to such subject a therapeutically effective amount of a compound according to formula (I), in particular leukemia, colon cancer, and breast cancer.
  • Each of the three subunits (7, 15, and 22) used to assemble meayamycin (1) or its analogs was derived from chiral pool starting intermediates such that all 8 chiral centers are introduced or controlled by chiral centers found in readily available, inexpensive starting materials, as shown in the Retrosynthetic Analysis below.
  • DMP Dess-Martin periodinane
  • BocNH-L-Thr derived variant of Garner's aldehyde, available in three steps from BocNH-L-Thr (1 equiv MeONHMe, 1.2 equiv EDCI, 1.2 equiv HOBt, 2 equiv (iPr )NEt, CH 2 CI 2 , 25 °C, 22 h; 0.2 equiv PPTS, 10 equiv MeC(OMe) 2 Me, THF, reflux, 18 h, 88% for two steps) including the reported DIBAL-H reduction of the Weinreb amide (2 equiv DIBAL-H, CH 2 CI 2 , -78 °C, 3 h) (Ref. 20).
  • L1210 is a murine lymphocytic leukemia cell line.
  • HCT116 and HCT116/VM46 are human colon cancer cell lines, with the latter being a multi-drug resistant variant of the former.
  • MCF-7 is a human breast cancer cell line.
  • aqueous layer was extracted with CH2CI2 (3 x 150 mL) and the combined organic layer was washed with saturated aqueous NaHCC>3, saturated aqueous NaCI, dried over Na 2 SO4, filtrated and concentrated under reduced pressure provided the amide as a yellow oil.
  • the ester 18 was immediately taken up in MeOH (12 mL), PPTS (170 mg, 0.68 mmol, 0.1 equiv) was added and the mixture was warmed at reflux for 2 h. After this time, the reaction mixture was cooled, diluted with Et 2 O (15 mL), washed with saturated aqueous NaCI (5 mL), dried over Na 2 SO 4 , filtered and concentrated.
  • the ester 21 (210 mg, 0.98 mmol, 1.0 equiv) was stirred in TFA/CH2CI2 (1.5 mL of a 10% solution) for 2 h before the solvent was removed in vacuo.
  • the crude material was purified by column chromatography (Si0 2 , 80% EtOAc in hexanes) to give 22 (152 mg, 0.96 mmol, 98%) as a dear oil: [ ⁇ ] D 2 +21 (c 1.0, CHCI3); 3 H NMR (600 MHz, CDCI3) Mé 26 (bs, 1H), 6.26 - 6.20 (m, 2H),
  • Methyltriphenylphosphonium bromide (687 mg, 1.92 mmol) in THF (1.3 mL) was treated with 1 M KO l Bu in THF (1.73 mL, 1.73 mmol) at 0 °C and the solution was stirred for 1 h at 0 °C.
  • a solution of 29 (338.1 mg, 0.962 mmol) in THF (3 mL) was add dropwise to the Wittig reagent solution at 0 °C.
  • the reaction mixture was stirred for 12 h at 23 °C before being quenched with the addition of saturated aqueous NH4CI. After separation of the organic layer, the aqueous layer was extracted three times with EtOAc.
  • reaction mixture was stirred for 12 h at 23 °C, before being quenched with the addition of saturated aqueous NH4CI. After separation of organic layer, the aqueous layer was extracted three times with EtOAc. The combined organic layer was washed with saturated aqueous NaHCC>3 and saturated aqueous NaCI, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure.
  • Tetra-n-butylammonium fluoride (Bu 4 NF, 1.0 M in THF, 0.017 mL, 0.017 mmol, 1.2 equiv) was added to a solution of 34 (10 mg, 0.014 mmol, 1.0 equiv) in THF (0.5 mL) at 0 ° C. After stirring for 2 h, the reaction mixture was concentrated in vacuo.
  • the alcohol S2 was prepared following a previously described procedure (Ref. 19) from 30 (K2CO3, MeOH, 0 °C, 95%) and used crude to prepare the following derivatives without further characterization.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/US2021/026408 2020-04-09 2021-04-08 Meayamycin analogues and methods of use Ceased WO2021207511A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US17/916,947 US20230159552A1 (en) 2020-04-09 2021-04-08 Meayamycin and its analogues, methods for their preparation, and methods of use
KR1020227038786A KR20220166828A (ko) 2020-04-09 2021-04-08 메야마이신 유사체 및 그의 사용 방법
CN202180027149.7A CN115698018A (zh) 2020-04-09 2021-04-08 美亚霉素类似物和使用方法
JP2022561608A JP2023521135A (ja) 2020-04-09 2021-04-08 メアヤマイシン類似体および使用方法
EP21722684.4A EP4132934A1 (en) 2020-04-09 2021-04-08 Meayamycin analogues and methods of use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063007564P 2020-04-09 2020-04-09
US63/007,564 2020-04-09

Publications (1)

Publication Number Publication Date
WO2021207511A1 true WO2021207511A1 (en) 2021-10-14

Family

ID=75747102

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/026408 Ceased WO2021207511A1 (en) 2020-04-09 2021-04-08 Meayamycin analogues and methods of use

Country Status (6)

Country Link
US (1) US20230159552A1 (https=)
EP (1) EP4132934A1 (https=)
JP (1) JP2023521135A (https=)
KR (1) KR20220166828A (https=)
CN (1) CN115698018A (https=)
WO (1) WO2021207511A1 (https=)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR901465A (fr) 1944-01-22 1945-07-27 Perfectionnements aux assemblages de bois, notamment pour charpentes, ainsi qu'aux procédés et aux machines pour l'obtention de ces assemblages
FR901464A (fr) 1943-01-23 1945-07-27 Boehringer & Soehne Gmbh Procédé d'obtention de vanilline
FR901463A (fr) 1943-02-27 1945-07-27 Bremshey & Co Dispositif pour la fixation des lames de bois du siège proprement dit et du dossier des sièges en tubes d'acier
US20080096879A1 (en) * 2006-09-08 2008-04-24 University Of Pittsburgh-- Of The Commonwealth System Of Higher Education Synthesis of fr901464 and analogs with antitumor activity
WO2015077370A1 (en) * 2013-11-19 2015-05-28 Purdue Research Foundation Anti-cancer agents and preparation thereof
US20150307512A1 (en) 2012-12-21 2015-10-29 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Synthesis of fr901464 and analogs with antitumor activity

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009031999A1 (en) * 2007-09-07 2009-03-12 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Fr901464 and analogs with antitumor activity and method for their preparation
CN105121421B (zh) * 2012-11-05 2020-10-02 辉瑞公司 司普力西欧他汀类似物
JP2019524650A (ja) * 2016-06-08 2019-09-05 ウィリアム マーシュ ライス ユニバーシティＷｉｌｌｉａｍ Ｍａｒｓｈ Ｒｉｃｅ Ｕｎｉｖｅｒｓｉｔｙ タイランスタチンａの誘導体、それについての治療方法および合成方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR901464A (fr) 1943-01-23 1945-07-27 Boehringer & Soehne Gmbh Procédé d'obtention de vanilline
FR901463A (fr) 1943-02-27 1945-07-27 Bremshey & Co Dispositif pour la fixation des lames de bois du siège proprement dit et du dossier des sièges en tubes d'acier
FR901465A (fr) 1944-01-22 1945-07-27 Perfectionnements aux assemblages de bois, notamment pour charpentes, ainsi qu'aux procédés et aux machines pour l'obtention de ces assemblages
US20080096879A1 (en) * 2006-09-08 2008-04-24 University Of Pittsburgh-- Of The Commonwealth System Of Higher Education Synthesis of fr901464 and analogs with antitumor activity
US7825267B2 (en) 2006-09-08 2010-11-02 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Synthesis of FR901464 and analogs with antitumor activity
US20150307512A1 (en) 2012-12-21 2015-10-29 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Synthesis of fr901464 and analogs with antitumor activity
WO2015077370A1 (en) * 2013-11-19 2015-05-28 Purdue Research Foundation Anti-cancer agents and preparation thereof

Non-Patent Citations (44)

* Cited by examiner, † Cited by third party
Title
"Activities against experimental tumors in mice and mechanism of action", J. ANTIBIOT., vol. 49, 1996, pages 1204 - 1211
"Second generation", TETRAHEDRON, vol. 62, 2006, pages 1378 - 1389
"spliceostatin A and evaluation of splicing activity of key derivatives", J. ORG. CHEM., vol. 79, 2014, pages 5697 - 5709
"spliceostatin A: Potent inhibitors of spliceosome", ORG. LETT., vol. 15, 2013, pages 5088 - 5091
"Total synthesis, proof of structure, and evaluation of synthetic analogues", J. AM. CHEM. SOC., vol. 123, 2001, pages 9974 - 9983
AKWABOAH, D. C.WU, D.FORSYTH, C.: "Stereoselective synthesis of the C1-C9 and C11-C25 fragments of amphidinolides C, C2, C3, and F.", ORG. LETT., vol. 19, 2017, pages 1180 - 1183
ALBERT, B. J.MCPHERSON, P. A.O'BRIEN, K.CZAICKI, N. L.DESTEFINO, V.OSMAN, S.LI, M.BILLY W. DAY, B. W.GRABOWSKI, P. J.MOORE, M. M.: "Meayamycin inhibits pre-mRNA splicing and exhibits picomolar activity against multidrug resistant cells", MOL. CANCER THER., vol. 8, 2009, pages 2308 - 2318, XP002752878, DOI: 10.1158/1535-7163.MCT-09-0051
ANNUNZIATA, R.CINQUINI, M.COZZI, F.DONDIO, G.RAIMONDI, L.: "Intramolecular nitrile oxide cycloaddition on chiral olefins: A stereocontrolled approach to β-keto! precursors", TETRAHEDRON, vol. 43, 1987, pages 2369 - 2380
BOGER, D. L.BROTHERTON, C. E.: "Total synthesis of azafluoranthene alkaloids: Rufescine and imeluteine", J. ORG. CHEM., vol. 49, no. 49, 1984, pages 4050 - 4055
BONNAL, S.VIGEVANI, L.VALCARCEL, J.: "The spliceosome as a target of novel antitumour drugs", NAT. REV. DRUG DISCOVERY, vol. 11, 2012, pages 847 - 859, XP055189513, DOI: 10.1038/nrd3823
CHEM. - EUR. J., vol. 17, 2011, pages 895 - 904
CRIMMINS, M. T.JACOBS, D. L.: "Asymmetric total synthesis of pyranicin", ORG. LETT., vol. 11, 2009, pages 2695 - 2698
DESTERRO, J.BAK-GORDON, P.CARMO-FONSECA, M.: "Targeting mRNA processing as an anticancer strategy", NAT. REV. DRUG DISCOVERY, 2019
GHOSH, A. K.REDDY, G. C.KOVELA. S.RELITTI, N.URABE, V. K.PRICHARD, B. E.JURICA, M. S.: "Enantioselective synthesis of a cyclopropane derivative of spliceostatin A and evaluation of bioactivity", ORG. LETT., vol. 20, 2018, pages 7293 - 7297
GHOSH, A. K.REDDY, G. C.MACRAE, A. J.JURICA, M. S.: "Enantioselective synthesis of spliceostatin G and evaluation of bioactivity of spliceostatin G and its methyl ester", ORG. LETT., vol. 20, 2018, pages 96 - 99
GHOSH, A. K.VEITSCHEGGER, A. M.NIE, S.RELITTI, N.MACRAE, A. J.JURICA, M. S.: "Enantioselective synthesis of thailanstatin A methyl ester and evaluation of in vitro splicing activity", J. ORG. CHEM., vol. 83, 2018, pages 5187 - 5198
GRELA, K.HARUTYUNYAN, S.MICHROWSKA, A.: "A highly efficient ruthenium catalyst for metathesis reactions", ANGEW. CHEM., INT. ED., vol. 41, 2002, pages 4038 - 4040, XP002278573, DOI: 10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0
HE, H.RATNAYAKE, A. S.JANSO, J. E.HE, M.YANG, H. Y.LOGANZO, F.SHOR, B.O'DONNELL, C. J.KOEHN, F. E.: "Cytotoxic spliceostatins from Burkholderia sp. and their semisynthetic analogues", J. NAT. PROD., vol. 77, 2014, pages 1864 - 1870, XP055451569, DOI: 10.1021/np500342m
J. AM. CHEM. SOC., vol. 128, 2006, pages 2792 - 2793
J. AM. CHEM. SOC., vol. 129, 2007, pages 2648 - 2659
J. ANTIBIOT., vol. 50, 1997, pages 96 - 99
J. ANTIBIOT., vol. 66, 2013, pages 555 - 558
J. SYNTH. ORG. CHEM., JPN., vol. 65, 2007, pages 119 - 126
K. C. NICOLAOU ET AL: "Total Syntheses of Thailanstatins A-C, Spliceostatin D, and Analogues Thereof. Stereodivergent Synthesis of Tetrasubstituted Dihydro- and Tetrahydropyrans and Design, Synthesis, Biological Evaluation, and Discovery of Potent Antitumor Agents", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 140, no. 26, 5 July 2018 (2018-07-05), US, pages 8303 - 8320, XP055674503, ISSN: 0002-7863, DOI: 10.1021/jacs.8b04634 *
KAIDA, D.MOTOYOSHI, H.TASHIRO, ENOJIMA, T.HAGIWARA, M.ISHIGAMI, K.WATANABE, H.KITAHARA, T.YOSHIDA, T.NAKAJIMA, H.: "Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA", NAT. CHEM. BIOL., vol. 3, 2007, pages 576 - 578
LAGISETTI, C.PALACIOS, G.GORONGA, T.FREEMAN, B.CAUFIELD, W.WEBB, T. R.: "Optimization of antitumor modulators of pre-mRNA splicing", J. MED. CHEM., vol. 56, 2013, pages 10033 - 10044
LAGISETTI, C.POURPAK, A.GORONGA, T.JIANG, Q.CUI, X.HYLE, J.LAHTI, J. M.MORRIS, S. W.WEBB, T. R.: "Synthetic mRNA splicing modulator compounds with in vivo antitumor activity", J. MED. CHEM., vol. 52, 2009, pages 6979 - 6990
LIU, X.BISWAS, S.BERG, M. G.ANTAPLI, C. M.XIE, F.WANG, Q.TANG, M.-C.TANG, G.-L.ZHANG, L.DREYFUSS, G.: "Genomics-guided discovery of thailanstatins A, B and C as pre-mRNA splicing inhibitors and anti-proliferative agents from Burkholderia thailandensis MSMB43", J. NAT. PROD., vol. 76, 2013, pages 685 - 693
LO, C.-W.KAIDA, D.NISHIMURA, S.MATSUYAMA, A.YASHIRODA, Y.TAOKA, H.ISHIGAMI, K.WATANABE, H.NAKAJIMA, H.TANI, T.: "Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 364, 2007, pages 573 - 577, XP027016280, DOI: 10.1016/j.bbrc.2007.10.029
MAKOWSKI, K.VIGEVANI, L.ALBERICIO, F.VALCARCEL, J.ALVAREZ, M.: "Sudemycin K: A synthetic antitumor splicing inhibitor variant with improved activity and versatile chemistry", ACS CHEM. BIOL., vol. 12, 2017, pages 163 - 173, XP055724549, DOI: 10.1021/acschembio.6b00562
MASSAD, S. K.HAWKINS, L. D.BAKER, D. C.: "A series of (25)-2-0-protected-2-hydroxypropanals (L-lactaldehydes) suitable for use as optically active intermediates", J. ORG. CHEM., vol. 48, 1983, pages 5180 - 5182
MED. CHEM. COMMUN., vol. 2, 2011, pages 38
MICHROWSKA, A.BUJOK, R.HARUTYUNYAN, S.SASHUK, V.DOLGONOS, G.GRELA, K.: "Nitro-substituted Hoveyda-Grubbs ruthenium carbenes: enhancement of catalyst activity through electronic activation", J. AM. CHEM. SOC., vol. 126, 2004, pages 9318 - 9325
NICOLAOU, K. C.RHOADES, D.KUMA, S. M.: "Total syntheses of thailanstatins A-C, spliceostatin D, and analogues thereof. Stereodivergent synthesis of tetrasubstituted dihydro- and tetrahydropyrans and design, synthesis, biological evaluation, and discovery of potent antitumor agents", J. AM. CHEM. SOC., vol. 140, 2018, pages 8303 - 8320, XP055674503, DOI: 10.1021/jacs.8b04634
NICOLAOU, K. C.RHOADES, D.LAMANI, M.PATTANAYAK, MANAS R.KUMAR, S. M.: "Total Synthesis of Thailanstatin A.", J. AM. CHEM. SOC., vol. 138, 2016, pages 7532 - 7535, XP055627925, DOI: 10.1021/jacs.6b04781
PRABHAKAR, P.RAJARAM. S.REDDY, D. K.SHEKAR, V.VENKATESWARLU, Y.: "Total Synthesis of the phytotoxic stagonolides A and B", TETRAHEDRON:ASYMMETRY, vol. 21, 2010, pages 216 - 221, XP026939548, DOI: 10.1016/j.tetasy.2010.01.010
SAMI OSMAN ET AL: "Structural Requirements for the Antiproliferative Activity of Pre-mRNA Splicing Inhibitor FR901464", CHEMISTRY - A EUROPEAN JOURNAL, vol. 17, no. 3, 19 November 2010 (2010-11-19), pages 895 - 904, XP055356284, ISSN: 0947-6539, DOI: 10.1002/chem.201002402 *
SCHOLL, M.DING, S.LEE, C. W.GRUBBS, R. H.: "Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands", ORG. LETT., vol. 1, 1999, pages 953 - 956
SMITH, A.B., IIIHAN, QBRESLIN, P. A. S.BEAUCHAMP, G. K.: "Synthesis and Assignment of Absolute Configuration of (-)-Oleocanthol: A Potent, Naturally Occurring Non-Steroidal Anti-inflammatory and Anti-oxidant Agent Derived from Extra Virgin Olive Oils", ORG. LETT., vol. 7, 2005, pages 5075 - 5078
SRINIVAS, B.SRIDHAR, R.RAO, K. R.: "Stereoselective total synthesis of (+)-varitriol", TETRAHEDRON, vol. 66, 2010, pages 8527 - 8535, XP027382444
TAXONOMY: "fermentation, isolation, physicochemical properties and biological activities", J. ANTIBIOT., vol. 49, 1996, pages 1196 - 1203
TETRAHEDRON LETT., vol. 42, 2001, pages 8207 - 8210
THOMPSON, C. F.JAMISON, T. F.JACOBSEN, E. N.: "Total synthesis of FR901464. Convergent assembly of chiral components prepared by asymmetric catalysis", J. AM. CHEM. SOC., vol. 122, 2000, pages 10482 - 10483
WILSON, Z. E.FENNER, S.LEY, S. V.: "Total syntheses of linear polythiazole/oxazole plantazolicin A and its biosynthetic precursor plantazolicin B", ANGEW. CHEM. INT. ED., vol. 54, 2015, pages 1284 - 1288

Also Published As

Publication number Publication date
KR20220166828A (ko) 2022-12-19
EP4132934A1 (en) 2023-02-15
US20230159552A1 (en) 2023-05-25
CN115698018A (zh) 2023-02-03
JP2023521135A (ja) 2023-05-23

Similar Documents

Publication Publication Date Title
Ireland et al. Convergent synthesis of polyether ionophore antibiotics: synthesis of the spiroketal and tricyclic glycal segments of monensin
Fuwa et al. An enantioselective total synthesis of aspergillides A and B
Hall et al. Transannular Diels-Alder/Intramolecular Aldol Tandem Reaction as a Stereocontrolled Route to (+)-Aphidicolin and its Isosteric C8-Epimer1
Díez et al. The use of butane diacetals of glycolic acid as precursors for the synthesis of the phytotoxic calmodulin inhibitor herbarumin II
Chang et al. Divergent total synthesis of aspinolides B, E and J
EP4132934A1 (en) Meayamycin analogues and methods of use
Formentín et al. Stereoselective synthesis of a C19–C26 fragment of amphidinolides G and H
Thakur et al. The stereoselective total synthesis of (−)-achaetolide
Pilli et al. The stereochemistry of the Nozaki-Hiyama-Kishi reaction and the construction of 10-membered lactones. The enantioselective total synthesis of (-)-decarestrictine D
Reddy et al. Stereoselective total synthesis of multiplolide A and of a diastereoisomer
López et al. Total synthesis of (+)-massarinolin B and (+)-4-epi-massarinolin B, fungal metabolites from Massarina tunicata
Qiu Progress Towards the Total Synthesis of Curvulamine
Reddipalli et al. Stereoselective synthesis of (−)-α-conhydrine
Singh Yadav et al. Formal Total Synthesis of Stevastelins B and B3
Hudlicky Synthetic Studies on Bielschowskysin
Bischoff Synthesis of cryptophycin B, arenastatin A, AI-77-B, and salicylihalamide A
Li Chain Assembly Tactics for Efficient Syntheses of Callyspongiolide and Portimine
US20040235939A1 (en) Synthesis of peloruside a and analogs thereof for use as antitumor agents
Markaj Synthetic Efforts Toward New Splicing Modulators
Afeke Re2O7-Mediated Spirocyclic Ether Synthesis from Acyclic Precursors: Synthesis and H2O2-Mediated Targeted Cellular Release of a Pederin Analogue
Roushanbakhti Synthesis of the EFG-ring system of pectenotoxin-4
Vadhadiya Studies toward the total synthesis of (+)-stagonolide D, mangiferaelactone, cytospolide E and sinenside A
Knutson A versatile method for the synthesis of α, β unsaturated lactones and the total asymmetric total synthesis of (−)-pironetin
Lei Development of syn-1, 3-diol methodologies and their applications to biologically active molecules
Velazquez Synthetic studies towards the synthesis of callipeltosides and aurisides

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21722684

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2022561608

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20227038786

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2021722684

Country of ref document: EP

Effective date: 20221109