Cyclization of 3-amino acids

As a rule, the synthesis of (3-lactams by cyclization of (3-amino acids such as (132) is impeded by Bayer strain and adverse conformational effects.117 By contrast, the conversion of (3-amino acids into (3-lactams by the Ugi reaction occurs with ease and in good yield.55-118... 

P-Lactam Cyclization. Cyclization of 3-amino acids to p-lactams is efficiently effected by treatment wi th BOP (eq 8) The... 

Ohtani, B., Iwai, K., Kominami, H., Matsuura, T., Kera, Y., and Nishimoto, S. (1995) Titanium(IV) oxide photocatalyst of ultra-high activity for selective N-cyclization of an amino acid in aqueous suspensions. Chemical Physics Letters, 242 (3), 315-319. 

Studies of the intramolecular cyclization of P-amino acids have included the use of camphor-derived oxazoline A-oxide 66 and a [3+2] cycloaddition reaction as a step in the formation of the amino acid with the required stereochemistry <00OL1053, OOEJOC1595>. A diastereoselective synthesis of a ip-methylcarbapenem intermediate utilises a cyclization of a P-amino acid <99CC2365>. 

The title compounds were obtained by cyclization of 3-amino-2-hydroxyquinazolin-4-ones (391) (86MI5 88MI2) or 1-substituted 2-hydrazinoquinazolin-4-ones (311) [83EGP(D)203545 84PHA867] with nitrous acid. In the latter case, it was necessary to block AM in order to direct the cyclization towards the less nucleophilic N-3 of the quinazoline ring. 

Cyclization of 3-indolylacrylic acid derivatives 200 and 201, obtained on interaction of 2-methylindole with the enol acetate of acetoacetic ester or with j8-amino-/3-methylacrylonitrile, leads to benzo[crf]indole-5-ones 202 (Y = O) or their nitrogen analogs 202 (Y = NH) (78TL4051). 

To build up the desired cyclic key precursors, containing an amide bond as an anchor to connect the triazole moiety, different strategies can be pursued. Cyclization of y-amino acids directly yields pyrroli-dones, whereas P-amino alcohols allow access to two different chiral bicyclic frameworks. They can form either oxazolidin-2-ones (Enders and Kallfass 2001) or morpholinones upon treatment with phosgene or chloro acetylchloride, respectively (Scheme 3). 

The synthesis of [3-lactones has received considerable attention6 since the first representative of this class of heterocycles was prepared in 1883. Classical routes to (3-lactones generally involved the cyclization of (3-halocarboxylate salts6 and the related "deaminative cyclization that occurs upon diazotization of [3-amino acids.9 p-Hydroxy acids undergo a similar cyclization under Mitsunobu conditions,10 and the... 

The isomeric 1-suhstituted imidazole-5-carboxylates are made by cyclization of 3-amino-2-alkylaminopropanoic acids with triethyl orthoformate followed by active manganese dioxide oxidation of the imidazoline product (see Section 3.1.1), or from IV-substituted glycine esters, which are formylated, converted into the enolates and then condensed with potassium thiocyanate... 

The cyclization of a-amino-acid amides with phosphorus(v) dichlorides gives 2,4-dioxo- and 4-oxo-2-thiono-l,3,2-diazaphospholidines (46), ... 

Oxidative cyclization of 3-amino-thioacrylic acid-amides, -esters or 2-amino-l-alkenyl-thioke tones ... 

Oxidative Cyclization of 3-Amino-Thioacrylic Acid-Amides, -Esters or 2-Amino-l-A Ikenyl- Thioketones... 

Synthesis from o-xylonolactone A synthesis of (25, 3-, 4A)-3,4-dihydroxy-proline (2) from 2,5-dibromo-2,5-dideoxy-D-xylono-l,4-lactone (77) has been reported (Scheme 11). ° Compound77 was reacted with sodium azide to give a 5 1 mixture of azides 78 and 79 in 95% yield. Hydrogenation of 78 afforded 2-amino-5-bromo-2,5-dideoxy-D-lyxono-1,4-lactone (80), which upon treatment with aqueous Ba(OH)2 led to spontaneous cyclization of the amino acid 81 to afford 2 in 60% yield. 

Lactamization. A key step in the first total synthesis of a maytansenoid, macrolactams with antitumor activity, involved cyclization of the amino acid 1. This reaction was effected by conversion of the acid into the soluble tetra-n-butylammonium salt and addition of this salt to a solution of mesitylenesulfonyl chloride and diisopropylethylamine in benzene (3 hours, 35°). The lactam 2 was... 

This reaction was first reported by Breckpot in 1923. It is the synthesis of )0-lactam via the cyclization of esters of /3-amino acids with Grignard reagent and is known as the Breckpot -lactam synthesis. This reaction has been modified to form )0-lactam by the treatment of )0-amino acid with Mukaiyama s reagent, or the /3-amino ester with /V-methyl pyridinium salt." ... 

Pyrazolo-[3,4-i/]- and -[5,l-6]-thiazoles [CsNS-CaNa].—Cyclization of 3-amino-2-methylthiazolium hydrogen sulphate with acetic anhydride yields the pyrazolo-[5,l-fe]thiazole (52), while condensation of the 3-mercapto-l,2-dihydro-pyrazoles (53) with chloroacetic acid gives compounds (54). ... 

Scheme 3.113 Bergman cyclization of acyclic amino acid derived enediynes leading to 2,3-dihydrobenzo[/]isoindoles.

Isoxazolidinones have been prepared by the cyclization of ethyl 3-O-hydroxyl-aminopropionate and by the cyclization of a-chloropropionhydroxamic acid (62HQ17)1, p. 7). 3-Isoxazolidinones can also be prepared by the hydrolysis of 3-alkoxy- or 3-amino-2-isoxazolines or 2-isoxazolinium salts (Scheme 159) (74BSF1651, 62G501). 

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

---