| Record 9371 View: Standard | Glossary HistCite Guide |
|
Author(s): Delgado O; Muller HM; Bach T
Title: Concise total synthesis of the thiazolyl peptide antibiotic GE2270 A
Source: CHEMISTRY-A EUROPEAN JOURNAL 14 (8): 2322-2339
Date: 2008
Document Type: Journal : Review
DOI:
Language: English
Comment:
Address: Tech Univ Munich, Lehrstuhl Organ Chem 1, D-85747 Garching, Germany.
Reprint: Bach, T, Janssen Cilag Med Chem Dept, Jarama 75, Toledo 45007, Spain.
E-mail: thorsten.bach@ch.tum.de
Author Keywords: antibiotics; cross-coupling; macrocycles; natural products; total
synthesis
KeyWords Plus: CROSS-COUPLING REACTIONS; FRAGMENT-A-C; BACTERIAL PROTEIN-SYNTHESIS;
CARBON BOND FORMATION; ELONGATION-FACTOR TU; KEY BUILDING-BLOCKS;
MICROCOCCIN-P; STRUCTURE ELUCIDATION; CONVENIENT SYNTHESIS; NATURAL-
PRODUCTS
Abstract: The potent antibiotic thiazolylpeptide GE2270 A was synthesized starting from N-tert-butyloxycarbonyl protected valine in a longest linear sequence of 20 steps and with an overall yield of 4.8%. Key strategy was the assembly of the 2,3,6-trisubstituted pyridine core by consecutive cross-coupling reactions starting from 2,6-dibromo-3-iodopyridine. The complete Southern fragment was installed by Negishi cross-coupling of 3-zincated 2,6-dibromopyridine at the terminal 2-iodothiazole of a trithiazole (87%). The substituent at C-6 representing the Northern part of the molecule was introduced in form of the truncated tertbutyl 2-bromothiazole-4-carboxylate after metalation to a zinc reagent by another Negishi cross-coupling (48%). Decisive step of the whole sequence was the macrocyclization to a 29-membered macrolactam, which was conducted as an intramolecular Stille cross-coupling occurring at C-2 of the pyridine core and providing the desired product in 75% yield. The required stannane was obtained by amide bond formation (87%) between a complex dithiazole fragment representing the Eastern part of GE2270 A and a 3,6-disubstituted 2-bromopyridine. Final steps included attachment of a serine-proline amide dipeptide to the Northern part of the molecule (65%), formation of the oxazoline ring and silyl ether deprotection (55% overall).
Cited References: AGUILAR E, 1994, TETRAHEDRON LETT, V35, P2473 AVENOZA A, 2002, J ORG CHEM, V67, P4241 AZIZIAN H, 1981, J ORGANOMET CHEM, V215, P49 BACH T, 1999, EUR J ORG CHEM SEP, P2045 BACH T, 2000, TETRAHEDRON LETT, V41, P1707 BACH T, 2001, ANGEW CHEM INT EDIT, V40, P3184 BACH T, 2001, ANGEW CHEM, V113, P3283 BACH T, 2002, CHEM-EUR J, V8, P5585 BACH T, 2002, J ORG CHEM, V67, P5789 BACH T, 2003, SYNTHESIS-STUTTG MAY, P925 BAGLEY MC, 2000, J AM CHEM SOC, V122, P3301 BAGLEY MC, 2004, ORG LETT, V6, P3401 BAGLEY MC, 2005, CHEM REV, V105, P685 BOUILLON A, 2002, TETRAHEDRON, V58, P2885 BROWN FK, 1989, J AM CHEM SOC, V111, P7328 BYCROFT BW, 1978, J CHEM SOC CHEM COMM, P256 CANIBANO V, 2001, SYNTHESIS-STUTTG NOV, P2175 CIUFOLINI MA, 1997, J ORG CHEM, V62, P3804 CLOUGH J, 2003, BIOORG MED CHEM LETT, V13, P3409 DALE JA, 1969, J ORG CHEM, V34, P2543 DELGADO O, 2006, J ORG CHEM, V71, P4599 DENG SJ, 2005, ORG LETT, V7, P299 DENHERTOG HJ, 1948, RECL TRAV CHIM PAY B, V67, P380 DOWNING SV, 1999, J ORG CHEM, V64, P826 DUNITZ JD, 1952, J AM CHEM SOC, V74, P995 FARINA V, 1997, ORG REACTIONS, V50, P1 FRIGERIO M, 1999, J ORG CHEM, V64, P4537 GABRIEL S, 1910, BER DTSCH CHEM GES 2, V43, P1283 GUTHMANN H, 2007, EUR J ORG CHEM 0201, P632 GUTTMANN S, 1958, HELV CHIM ACTA, V41, P1852 HANAN GS, 1997, CAN J CHEM, V75, P169 HANTZSCH A, 1889, LIEBIGS ANN CHEM, V250, P257 HARTMAN C, 1893, CHEM BER, V26, P1727 HECKMANN G, 2005, ANGEW CHEM INT EDIT, V44, P1199 HEFFRON SE, 2000, BIOCHEMISTRY-US, V39, P37 HILGENFELD R, 2000, RIBOSOME STRUCTURE F, P347 HUGHES RA, 2004, CHEM COMMUN 0421, P946 HUGHES RA, 2005, J AM CHEM SOC, V127, P15644 HUGHES RA, 2007, ANGEW CHEM, V119, P8076 KABURAGI Y, 2007, ORG LETT, V9, P723 KALININ VN, 1992, SYNTHESIS-STUTTG MAY, P413 KELLY TR, 1991, TETRAHEDRON LETT, V32, P4263 KELLY TR, 1996, J ORG CHEM, V61, P4623 KETTENRING J, 1991, J ANTIBIOT, V44, P702 KRAB IM, 2002, PROG NUCLEIC ACID RE, V71, P513 KUETHE JT, 2004, J ORG CHEM, V69, P7752 LAFARGUE P, 1995, HETEROCYCLES, V41, P947 LAGANIS ED, 1984, TETRAHEDRON LETT, V25, P5831 LENMAN MM, 1996, CHEM COMMUN 0107, P85 LI JJ, 2000, PALLADIUM HETEROCYCL MARZI E, 2001, EUR J ORG CHEM APR, P1371 MILSTEIN D, 1979, J AM CHEM SOC, V101, P4992 MOCEK U, 1993, J AM CHEM SOC, V115, P7557 MOCEK U, 1993, J AM CHEM SOC, V115, P7992 MOODY CJ, 1998, J CHEM SOC CHEM COMM, P2049 MORE JD, 2002, ORG LETT, V4, P3001 MULLER HM, 2007, ANGEW CHEM INT EDIT, V46, P4771 MULLER HM, 2007, ANGEW CHEM, V119, P4855 NEGISHI EI, 1977, J ORG CHEM, V42, P1821 NICOLAOU KC, 2002, ANGEW CHEM INT EDIT, V41, P1937 NICOLAOU KC, 2002, ANGEW CHEM INT EDIT, V41, P1941 NICOLAOU KC, 2002, ANGEW CHEM, V114, P2017 NICOLAOU KC, 2002, ANGEW CHEM, V114, P2021 NICOLAOU KC, 2003, ANGEW CHEM INT EDIT, V42, P3418 NICOLAOU KC, 2003, ANGEW CHEM, V115, P3540 NICOLAOU KC, 2004, ANGEW CHEM INT EDIT, V43, P5087 NICOLAOU KC, 2004, ANGEW CHEM INT EDIT, V43, P5092 NICOLAOU KC, 2004, ANGEW CHEM, V116, P5197 NICOLAOU KC, 2004, ANGEW CHEM, V116, P5202 NICOLAOU KC, 2005, ANGEW CHEM INT EDIT, V44, P1378 NICOLAOU KC, 2005, ANGEW CHEM INT EDIT, V44, P4442 NICOLAOU KC, 2005, ANGEW CHEM, V117, P1402 NICOLAOU KC, 2005, ANGEW CHEM, V117, P4516 NICOLAOU KC, 2005, J AM CHEM SOC, V127, P11159 NICOLAOU KC, 2005, J AM CHEM SOC, V127, P11176 NICOLAOU KC, 2006, ANGEW CHEM INT EDIT, V45, P7786 NICOLAOU KC, 2006, ANGEW CHEM, V118, P7950 OKUMURA K, 1996, CHEM LETT, P1025 OKUMURA K, 1998, B CHEM SOC JPN, V71, P1863 OKUMURA K, 1998, HETEROCYCLES, V48, P1319 OKUMURA K, 1999, B CHEM SOC JPN, V72, P1561 OKUMURA K, 1999, B CHEM SOC JPN, V72, P2483 OKUMURA K, 2000, HETEROCYCLES, V53, P765 PAGANO JF, 1956, ANTIBIOT ANNU, P554 PARMEGGIANI A, 2006, BIOCHEMISTRY-US, V45, P6846 PARMEGGIANI A, 2006, FEBS LETT, V580, P4576 PEDERSEN BS, 1978, B SOC CHIM BELG, V87, P223 PEYMAN A, 1993, ANGEW CHEM INT EDIT, V32, P1720 PEYMAN A, 1993, ANGEW CHEM, V105, P1852 PHILLIPS AJ, 2000, ORG LETT, V2, P1165 PRASAD ASB, 1997, TETRAHEDRON, V53, P7237 RIEGO E, 2005, SYNTHESIS-STUTT 0801, P1907 RISPENS MT, 1996, TETRAHEDRON, V52, P3521 SCHLOSSER M, 2005, ANGEW CHEM INT EDIT, V44, P376 SCHROTER S, 2005, SYNLETT 0801, P1957 SCHROTER S, 2005, TETRAHEDRON, V61, P2245 SELVA E, 1991, J ANTIBIOT, V44, P693 SELVA E, 1995, J ANTIBIOT, V48, P1039 SHEEHAN JC, 1961, J ORG CHEM, V26, P2525 SHIMANAKA K, 1994, J ANTIBIOT, V47, P1145 SHIMANAKA K, 1994, J ANTIBIOT, V47, P1153 SHIMANAKA K, 1994, J ANTIBIOT, V47, P668 SHIN C, 1998, CHEM LETT, P139 SOMOGYI L, 2001, TETRAHEDRON, V57, P1699 STEINBERG BA, 1956, ANTIBIOT ANNU, P562 STILLE JK, 1986, ANGEW CHEM INT EDIT, V25, P508 STILLE JK, 1986, ANGEW CHEM, V98, P504 SUZUKI T, 2001, HETEROCYCLES, V55, P835 TAKAHASHI T, 2002, J AM CHEM SOC, V124, P576 TAVECCHIA P, 1994, J ANTIBIOT, V47, P1564 TAVECCHIA P, 1995, TETRAHEDRON, V51, P4867 TRECOURT F, 2000, TETRAHEDRON, V56, P1349 TYMIAK AA, 1989, J ORG CHEM, V54, P1149 UNG AT, 1998, TETRAHEDRON-ASYMMETR, V9, P1395 VANDEPUTTE J, 1956, ANTIBIOT ANNU, P560 VONNUSSBAUM F, 2006, ANGEW CHEM INT EDIT, V45, P5072 WALKER J, 1977, J CHEM SOC CHEM COMM, P706 YANG W, 2003, ORG LETT, V5, P3131 |