1. A procedure for preparing an F-18 labeled aryl derivative comprising:
replacing the iodonium ylide group of a benzene derivative containing an iodonium ylide group with a no-carrier-added F-18 fluoride ion.
2. The procedure of claim 1 wherein the benzene derivative containing an iodonium ylide group is selected from the group comprising:
3. The procedure of claim 1 wherein the benzene derivative containing an iodonium ylide group is listed in the left hand column of the table below and the F-18 containing any derivative produced therefrom is listed in the corresponding right hand column of the table below:
Phenyl iodonium
ylide
Product
4. The procedure of claim 1 wherein the no-carrier-added F-18fluoride ion is produced by proton bombardment of 0-18water in a cyclotron body.
5. The procedure of claim 4 wherein:
an aqueous solution containing the F-18fluoride ion is treated with potassium carbonate and a ligand or tetraalkylammonium bicarbonate,
and the treated solution is evaporated to dryness to form a dry composition containing an F-18fluoride ion labeled compounds.
6. The procedure of claim 5 wherein the dry composition containing F-18fluoride ion labeled compounds is reacted with the benzene derivative containing an iodonium ylide group to form an F-18 fluoroaryl derivative.
7. The procedure of claim 6 wherein the F-18fluoroaryl derivative is purified to produce a >95% radiochemically pure F-18fluoroaryl derivative.
8. The procedure of claim 6 wherein the F-18fluoroaryl derivative is purified to produce a >99% radiochemically and chemically pure product.
9. A procedure for preparing compounds labeled with a radiation emitting halogen moiety comprising:
replacing the halogen group in an aryl derivative containing a pendent halogen group by an isotope ion of a halogen suitable for labeling purposes to form a radiation emitting halogen labeled aryl derivative,
the radiation emitting ion being free of an ion carrier.
10. The procedure of claim 9 wherein the pendent halogen group is chloride or bromide.
11. 2,2-Dimethyl-4,6-dioxo-1,3-dioxan-5-N-di(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-L-phenylalanine ethyl ester-6-iodoniumylide.
12. A process for producing 2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-N-di(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-L-phenylalanine ethyl ester-6-iodonium ylide comprising:
(a) forming N-di(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-6-iodo-L-phenylalanine ethyl ester by reacting N-(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-6-iodo-L-phenylalanine ethyl ester with di-tert-butyldicarbonate,
(b) reacting the product of step a) above with dimethyldioxirane in acetone-acetic acid mixture to form N-di(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-6-(diacetoxy)iodo-L-phenylalanine ethyl ester, and
(c) exposing the product of step b) above to 2,2-dimethyl-4,6-dioxo-1,3-dioxane to form 2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-N-di(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-L-phenylalanine ethyl ester-6-iodonium ylide.
13. A process for forming 6-F-18fluoro-L-dopa comprising:
(a) preparing an F-18 labeled aryl derivative comprising:
replacing the iodonium ylide group of a benzene derivative containing an iodonium ylide group with a no-carrier-added F-18 fluoride ion, said no-carrier-added F-18fluoride ion being produced by proton bombardment of O-18water in a cyclotron body,
treating an aqueous solution containing the F-18fluoride ion with potassium carbonate and a ligand or tetraalkylammonium bicarbonate,
and evaporating the treated solution to dryness to form a dry composition containing an F-18fluoride ion labeled compounds.
(b) reacting 2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-N-di(tert-butoxycarbonyl)-3,4-di-(tert-butoxycarbonyloxy)-L-phenylalanine ethyl ester-6-iodonium ylide with the dry composition containing the F-18fluoride ion labeled compounds, and
(c) treating the product of step b) above with a halogen acid.
14. A compound having the formula:
wherein R1 and R2 are hydroxyl protecting lower alkyl (methyl, ethyl) groups or benzyl or tert-butoxycarbonyl groups,
R3 and R4 are amine protecting acetoxy, trifluoroacetoxy or tert-butoxycarbonyloxy groups,
R5 is carboxylic acid protecting methyl, ethyl, tert-butyl, or benzyl groups,
X\u2550CH2, O, S, NCH3, NCH2Ph and
Y\u2550CH2, C(CH3)2, C\u2550O
15. The compound of claim 14 where R1 and R2 are (CH3)3COCO, R3 and R4 are (CH3)3COCO, X\u2550O and Y\u2550C(CH3)2.
16. A procedure for the preparation of iodonium ylide analogs having the formula:
wherein:
R1\u2550R2\u2550R3\u2550OCOOC(CH3)3, or
R1\u2550R2\u2550OCOOC(CH3)3, OCH3 and R3\u2550COCH3, COOCH2Ph, or
R1\u2550H; R2\u2550OCOOC(CH3)3, OCH3 and R3\u2550COCH3, COOCH2Ph, or
R1\u2550OCOOC(CH3)3, OCH3; R2\u2550H and R3\u2550COCH3, COOCH2Ph, and
X\u2550CH2, O, S, NCH3, NCH2Ph and
Y\u2550CH2, C(CH3)2, \u2550O
comprising:
hydrolyzing an ester group in a protected L-iododopa or L-iodotyrosine analogs, cyclizing an amino acid group therein,
oxidizing an iodo group therein into a diacetoxyiodo moiety and subsequently reacting the resultant compound with a cyclo 1,3-dicarbonyl derivative.
17. A method for the production of F-18 chiral analogs having the formula:
comprising the nucleophilic substitution of an iodonium ylide group in a chiral derivative having the formula
wherein:
R1\u2550R2\u2550R3\u2550OCOOC(CH3)3, or
R1\u2550R2\u2550OCOOC(CH3)3, OCH3 and R3\u2550COCH3, COOCH2Ph, or
R1\u2550H; R2\u2550OCOOC(CH3)3, OCH3 and R3\u2550COCH3, COOCH2Ph or
R1\u2550OCOOC(CH3)3, OCH3; R2\u2550H and R3\u2550COCH3, COOCH2Ph, and
X\u2550CH2, O, S, NCH3, NCH2Ph and
Y\u2550CH2, C(CH3)2, \u2550O
using dry heating or microwave heating for the nucleophilic substitution of the iodonium ylide group in said chiral derivative, providing a dry, anhydrous no-carrier-added F-18 fluoride ion, said F-18 fluoride ion being derived from a F-18KFKryptofix complex, F-18CsF or quaternary ammonium fluoride, the quaternary ammonium groups being selected from tetramethyl, yetraethyl, tetra n-butyl, and tetrabenzyl.
18. A method of producing F-18 labeled L-amino acids or D-amino acids having the formula:
wherein:
R4\u2550R5\u2550OH
R4\u2550H; R5\u2550OH
R4\u2550OH; R5\u2550H
comprising the acid hydrolysis of protected F-18 labeled D-chiral or L-chiral analogs respectively having the formula:
with the mineral acids HCl, HBr or HI under dry heating or microwave heating conditions wherein
R1\u2550R2\u2550R3\u2550OCOOC(CH3)3, or
R1\u2550R2\u2550OCOOC(CH3)3, OCH3 and R3\u2550COCH3, COOCH2Ph, or
R1\u2550H; R2\u2550OCOOC(CH3)3, OCH3 and R3\u2550COCH3, COOCH2Ph or
R1\u2550OCOOC(CH3)3, OCH3, R2\u2550H and R3\u2550COCH3, COOCH2Ph.
19. A procedure for the preparation of iodonium ylide derivatives having the formula
wherein:
R1\u2550R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3, or
R1=H and R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3, or
R1\u2550OCH2Ph, OCOOC(CH3)3, OCH3 and R2\u2550H and
X\u2550CH2, O, S, NCH3, NCH2Ph
Y\u2550CH2, C(CH3)2, \u2550O
comprising reacting:
with a chiral oxoimidazolidine auxiliary to produce a protected chiral amino acid derivatives, reacting the resultant compound with dimethyldioxirane in the presence of acetic acid to produce a diacetoxyiodo analog and subsequently reacting the diacetoxyiodo analog with a cyclo 1,3-dicarbonyl derivative.
20. A method for the production of F-18 chiral compounds having the formula
comprising the nucleophilic substitution of the iodonium ylide group in a chiral derivative having the formula
with dryanhydrous no-carrier-added F-18 fluoride ion using dry heating or microwave heating where the F-18 fluoride ion is derived from F-18KFKryptofix complex, F-18CsF or quaternary ammonium fluoride, the quaternary ammonium group being selected from tetramethyl, yetraethyl, tetra n-butyl, and tetrabenzyl and
R1\u2550R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3, or
R1=H and R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3, or
R1\u2550OCH2Ph, OCOOC(CH3)3, OCH3 and R2\u2550H and
X\u2550CH2, O, S, NCH3, NCH2Ph and
Y\u2550CH2, C(CH3)2, \u2550O
21. A method for producing F-18 labeled L-amino acids or D-amino acids having the formula
wherein:
R3\u2550R4\u2550OH or
R3\u2550H; R4\u2550OH or
R3\u2550OH; R4\u2550H
comprising acid hydrolysis, using mineral acids selected from the group consisting of HCl, HBr or HI, under dry heating or microwave heating conditions of protected F-18 labeled L-chiral or D-chiral analogs, respectively having the formula:
wherein:
R1\u2550R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3, or
R1=H and R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3, or
R1\u2550OCH2Ph, OCOOC(CH3)3, OCH3 and R2\u2550H
22. A procedure for the preparation of the iodonium ylides having the formula
comprising:
reacting
with a chiral pyrazine auxiliary to produce protected chiral amino acid derivatives, reacting the resultant compound with dimethyldioxirane in the presence of acetic acid to produce a diacetoxyiodo analog and subsequently reacting the diacetoxyiodo analog with the cyclo 1,3-dicarbonyl derivatives wherein:
R1\u2550R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3 or
R1=H; R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3 or
R1\u2550OCH2Ph, OCOOC(CH3)3, OCH3; R2\u2550H and
X\u2550CH2, O, S, NCH3, NCH2Ph and
Y\u2550CH2, C(CH3)2, \u2550O
23. A method for the production of F-18 chiral analogs having the formula
comprising the nucleophilic substitution of the iodonium ylide group in a chiral analog having the formula:
with dryanhydrous no-carrier-added F-18 fluoride ion using dry heating or microwave heating where the F-18 fluoride ion is derived from F-18KFKryptofix complex, F-18CsF or quaternary ammonium fluoride, the quaternary ammonium groups selected from tetramethyl, yetraethyl, tetra n-butyl, and tetrabenzyl wherein
R1\u2550R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3 or
R1=H; R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3 or
R1\u2550OCH2Ph, OCOOC(CH3)3, OCH3; R2\u2550H and
X\u2550CH2, O, S, NCH3, NCH2Ph and
Y\u2550CH2, C(CH3)2, \u2550O
24. A method for producing F-18 labeled L-amino acids having the formula
wherein:
R3\u2550R4\u2550OH
R3\u2550H; R4\u2550OH or
R3\u2550OH; R4\u2550H
comprising acid hydrolysis with mineral acids selected from the group consisting of HCl, HBr or HI under dry heating or microwave heating conditions of a protected F-18 labeled chiral analog having the formula
wherein:
R1\u2550R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3 or
R1=H; R2\u2550OCH2Ph, OCOOC(CH3)3, OCH3 or
R1\u2550OCH2Ph, OCOOC(CH3)3, OCH3; R2\u2550H
25. The processes of claim 12 for the preparation of
a) iodonium ylide containing amino acids having a D-configuration comprising utilizing D-chiral precursors, or
b) iodonium ylide containing amino acids having an L-configuration comprising utilizing-L-chiral precursors.
26. The methods of claim 17 for the preparation of
a) iodonium ylide containing amino acids having a D-configuration comprising utilizing D-chiral precursors, or
b) iodonium ylide containing amino acids having an L-configuration comprising utilizing-L-chiral precursors.
27. The methods of claim 20 for the preparation of
a) iodonium ylide containing amino acids having a D-configuration comprising utilizing D-chiral precursors, or
b) iodonium ylide containing amino acids having an L-configuration comprising utilizing-L-chiral precursors.
28. The methods of claim 23 for the preparation of
a) iodonium ylide containing amino acids having a D-configuration comprising utilizing D-chiral precursors, or
b) iodonium ylide containing amino acids having an L-configuration comprising utilizing-L-chiral precursors.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. The headlight for a motor vehicle with light unit for daytime and nighttime front navigation light and a supplemental distance light comprising:
a casing (5), provided at its front open end with a transparent cover (1) and on the inside with at least one optical module (3), with a light source (2) and with a connector (4), while between the casing (5) and the transparent cover (1) of the headlight is a supplemental light unit (7), wherein the light sources (61, 62) of the supplemental unit (7) are supplied with alternating electric current, for creation of the front nighttime navigation light when supplied with low electric current, or the front daytime navigation light when supplied with medium electric current, and for creation of a supplemental beam in addition to the distance light beam emerging from the optical module (3) when they are supplied with the highest electric current.
2. The headlight according to claim 1, wherein the alternating power supply of the light sources (61) of the supplemental unit (7) with low side scatter, primarily the ones used to create the supplemental distance beam for the distance light beam emerging from the optical module (3), is implemented by their gradual turning on.
3. The headlight according to claim 1, wherein the alternating power supply of the light sources (62) of the supplemental unit (7) with broad side scatter, primarily those used to create the front nighttime navigation light and the front daytime navigation light, is implemented by modulating the width of the electric pulse.
4. The headlight according to claim 1, wherein the light sources (61, 62) of the supplemental unit (7) are of LED andor bulb type, namely sources (61) with optics having small side scatter and sources (62) with optics having broad side scatter.
5. The headlight according to claim 1, wherein the optical module (3) is of reflector or projector type.
6. The headlight according to claim 1, wherein the light source (2) in the optical module (3) is a halogen bulb or high-pressure discharge
7. The headlight according to claim 1, wherein the light source (2) in the optical module (3) is of LED type.