Organic compounds -- part of the class 532-570 series – Organic compounds – Fatty compounds having an acid moiety which contains the...
Patent
1997-12-15
2000-07-04
Carr, Deborah D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Fatty compounds having an acid moiety which contains the...
C07C22700
Patent
active
060841125
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a method for the preparation of .omega.-aminoalkanoic acids, N-Boc protected .omega.-aminoalkanoic acids, and Boc-amino acid coupled .omega.-aminoalkanoic acids.
BACKGROUND OF THE INVENTION
.omega.-Aminoalkanoic acids have a wide variety of applications. One such use is as spacer molecules in solid phase peptide synthesis (SPPS). These spacer molecules serve to distance the growing peptide chains from the solid resin support allowing the supported biopolymers to be more accessible for subsequent chemical reactions. J. Org. Chem., 41, page 1350, (1976). Incorporation of such spacers can be important in the preparation of combinatorial libraries wherein large enzymes or antibodies are frequently used to assess the in-vitro activities of the pendant peptides. Minimization of restrictions exerted by the resin allows a more effective interaction between the protein and peptide, Immunomethods, 1, page 11, (1992).
For example, substituted 6-aminocaproic acid derivatives have been used to induce and maintain conformational rigidity in peptide fragments. The resulting cyclic peptidomimetic compounds have .beta.-turn structures. J. Am. Chem., 117, page 5169, (1995).
The .omega.-aminoalkanoic acids are also used in the covalent modification of antigenic peptides with lipophilic moieties such as aminohexadecanoic acid or lauric acid to enhance immunogenicity. For example, a laurylpetide adjuvant can be coupled to a 16 amino acid peptide from the V3 loop of the third hypervariable domain of the HIV-1 to envelope glycoprotein gp 120. This adjuvant-linked peptide stimulated elevated immune responses when compared to the peptide alone. J. Med. Chem., 38, page 459, (1995).
The .omega.-aminoalkanoic acids can also serve as useful synthetic "handles" for these adjuvants since these acids contain both amino and carboxylic termini which can be further derivatized.
Because of the many uses for .omega.-aminoalkanoic acids, there is a need in the art for a simple, inexpensive route to prepare these .omega.-aminoalkanoic acids and their derivatives. A number of methods for the preparations of .omega.-aminoalkanoic acids have been reported. The amine group on the .omega.-aminoalkanoic acids can be introduced by first converting a ketone to an oxime using hydroxylamine sulfonic acid. The .omega.-hydroxyimino acids formed are then reduced using Raney nickel to provide .omega.-aminoalkanoic acids. (French Patent 1,349,281, Jan. 7, 1964). The preparation of .omega.-aminoalkanoic acids by reduction of an organic acid with a terminal nitrile to an amine, with lithium aluminum hydride, has also been reported. The nitriles were prepared by conversion of an acid having a terminal group such as a halogen to a nitrile group. Chem. Tech., 8, page 187, (1956). Other methods require formation of an anhydride from an organic diacid followed by opening the anhydride with an azide. The intermediate compound was rearranged via a Schmidt rearrangement at an elevated temperature (50-60.degree.). Chem & Pharm. Bull., 7, page 99, (1959). Cyclic anhydrides have been opened with concentrated ammonium hydroxide followed by warming to about 50.degree. and addition of sodium hydroxide to provide the corresponding half amide. The half-amide can be converted to the corresponding .omega.-aminoalkanoic acid by Hofmann rearrangement using aqueous base and bromine. Chem. Ber., 89, page 117, (1956).
Boc protected .omega.-aminoalkanoic acids have been prepared from lactams that have been previously acylated with a t-butyloxycarbonyl acylating agent. The N-acylated lactam product can be treated with a base in aqueous tetrahydrofuran to provide the N-butoxycarbonyl .omega.-aminoalkanoic acids by hydrolysis. However, chromatographic purification of the N-butoxycarbonyl lactams is usually required. J. Org. Chem., 48, page 2424, (1983).
Aube et al. recently reported the synthesis Boc protected peptides of methyl substituted 6-aminohexanoic acid. A lactam was prepared and opened with hydrochloric acid solution. T
REFERENCES:
patent: Re24899 (1960-11-01), Green
patent: 2671451 (1954-03-01), Bolger
patent: 2828206 (1958-03-01), Rosenberg
patent: 2862918 (1958-12-01), Meyer et al.
patent: 2868740 (1959-01-01), Luce
patent: 2971916 (1961-02-01), Schleicher et al.
patent: 3016308 (1962-01-01), Macaulay
patent: 3052655 (1962-09-01), Fox et al.
patent: 3057344 (1962-10-01), Abella et al.
patent: 3076790 (1963-02-01), Fox et al.
patent: 3170802 (1965-02-01), Fukushima
patent: 3190837 (1965-06-01), Brynko et al.
patent: 3474777 (1969-10-01), Figge et al.
patent: 3491093 (1970-01-01), Pachter et al.
patent: 3565559 (1971-02-01), Sato
patent: 3567650 (1971-03-01), Bakan
patent: 3574832 (1971-04-01), Engel et al.
patent: 3576758 (1971-04-01), Emrick
patent: 3687926 (1972-08-01), Arima et al.
patent: 3725113 (1973-04-01), Chang
patent: 3748277 (1973-07-01), Wagner
patent: 3794561 (1974-02-01), Matsukawa et al.
patent: 3795739 (1974-03-01), Birkmayer et al.
patent: 3816404 (1974-06-01), Kablaoui et al.
patent: 3822348 (1974-07-01), Higashi et al.
patent: 3849550 (1974-11-01), Teitelbaum
patent: 3933873 (1976-01-01), Love et al.
patent: 3937668 (1976-02-01), Zolle
patent: 3939253 (1976-02-01), Bodor et al.
patent: 3956172 (1976-05-01), Saeki et al.
patent: 3962416 (1976-06-01), Katzen
patent: 3976773 (1976-08-01), Curran
patent: 4035507 (1977-07-01), Bodor et al.
patent: 4048268 (1977-09-01), Ludwig
patent: 4061466 (1977-12-01), Sjoholm et al.
patent: 4117801 (1978-10-01), Dannelly et al.
patent: 4147767 (1979-04-01), Yapel
patent: 4183849 (1980-01-01), Hansen
patent: 4199561 (1980-04-01), Roth et al.
patent: 4217370 (1980-08-01), Rawlings et al.
patent: 4238506 (1980-12-01), Stach et al.
patent: 4239635 (1980-12-01), Rieder
patent: 4239754 (1980-12-01), Sache et al.
patent: 4272506 (1981-06-01), Schwarzberg
patent: 4289759 (1981-09-01), Heavner et al.
patent: 4345588 (1982-08-01), Widder et al.
patent: 4348384 (1982-09-01), Horikoshi et al.
patent: 4351337 (1982-09-01), Sidman
patent: 4352883 (1982-10-01), Lim
patent: 4357259 (1982-11-01), Senyei et al.
patent: 4388304 (1983-06-01), Nyeki et al.
patent: 4393192 (1983-07-01), Curatolo et al.
patent: 4402856 (1983-09-01), Schnoring et al.
patent: 4402968 (1983-09-01), Martin
patent: 4405598 (1983-09-01), Brown
patent: 4442090 (1984-04-01), Kakeya et al.
patent: 4446138 (1984-05-01), Pack
patent: 4450150 (1984-05-01), Sidman
patent: 4457907 (1984-07-01), Porter
patent: 4460563 (1984-07-01), Calanchi
patent: 4462839 (1984-07-01), McGinley et al.
patent: 4462991 (1984-07-01), Higuchi et al.
patent: 4473620 (1984-09-01), Wu et al.
patent: 4483807 (1984-11-01), Asano
patent: 4492684 (1985-01-01), Goosen et al.
patent: 4518433 (1985-05-01), McGinley et al.
patent: 4590265 (1986-05-01), Bogan et al.
patent: 4608278 (1986-08-01), Frank
patent: 4613500 (1986-09-01), Suzuki et al.
patent: 4647455 (1987-03-01), De Bold
patent: 4666641 (1987-05-01), Fickat et al.
patent: 4671954 (1987-06-01), Goldberg
patent: 4673566 (1987-06-01), Goosen et al.
patent: 4683092 (1987-07-01), Tsang
patent: 4690786 (1987-09-01), Ninomiya et al.
patent: 4692284 (1987-09-01), Braden
patent: 4692433 (1987-09-01), Hostetler et al.
patent: 4703042 (1987-10-01), Bodor
patent: 4708952 (1987-11-01), Salatinjants
patent: 4745161 (1988-05-01), Saudek et al.
patent: 4753804 (1988-06-01), Iaccheri et al.
patent: 4757007 (1988-07-01), Satoh
patent: 4757024 (1988-07-01), Roper
patent: 4757066 (1988-07-01), Shiokari et al.
patent: 4766012 (1988-08-01), Valenti
patent: 4774320 (1988-09-01), Tagliabue et al.
patent: 4789734 (1988-12-01), Pierschbacher
patent: 4835312 (1989-05-01), Itoh et al.
patent: 4837381 (1989-06-01), Steber et al.
patent: 4844904 (1989-07-01), Hamaguchi et al.
patent: 4873087 (1989-10-01), Morishita et al.
patent: 4878942 (1989-11-01), Motegi et al.
patent: 4886663 (1989-12-01), Houghten
patent: 4895725 (1990-01-01), Kantor et al.
patent: 4897444 (1990-01-01), Byrnes et al.
patent: 4900730 (1990-02-01), Miyauchi
patent: 4908233 (1990-03-01), Takizawa et al.
Ho Koc-Kan
Leone-Bay Andrea
Carr Deborah D.
Emisphere Technologies Inc.
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