METHODS OF PRODUCING NOR-OPIOID AND NAL-OPIOID BENZYLISOQUINOLINE ALKALOIDS

1 . A nal-opioid compound does not contain one or more detectable impurities associated with chemical synthesis.

2 . The nal-opioid compound of claim 1 , wherein the nal-opioid is buprenorphine and the one or more impurities associated with chemical synthesis include 15,16-Dehydrobuprenorphine, 17,18-Dehydrobuprenorphine, 18,19-demethylbuprenorphine, 19,19′-Ethylbuprenorphine, 2,2′-Bisbuprenorphine, 3-Deshydroxybuprenorphine, 3-O-Methylbuprenorphine, 3-O-Methyl-N-cyanonorbuprenorphine, 3-O-Methyl-N-methylnorbuprenorphine, 6-O-Desmethylbuprenorphine, Buprenorphine N-oxide, N-But-3-enylnorbuprenorphine, N-But-3-enylnormethylbuprenorphine, N-Butylnorbuprenorphine, N-Methylbuprenorphine, Norbuprenorphine, and Tetramethylfuran buprenorphine.

3 . The nal-opioid compound of claim 1 , wherein the nal-opioid is oxymorphone and the one or more impurities associated with chemical synthesis include 1-Bromooxymorphone, 6-Beta oxymorphol, 10-Alpha-hydroxyoxymorphone, 10-Ketooxymorphone, 2,2-Bisoxymorphone, Noroxymorphone, Oxymorphone N-oxide, 10-Hydroxyoxymorphone, 4-Hydroxyoxymorphone, 8-Hydroxyoxymorphone, and Hydromorphinol.

4 . The nal-opioid compound of claim 1 , wherein the nal-opioid is naltrexone and the one or more impurities associated with chemical synthesis include 10-, 10-Ketonaltrexone, 14-Hydroxy-17-cyclopropylmethylnormorphinone, 2,2′-Bisnaltrexone, 3-Cyclopropylmethylnaltrexone, 3-O-Methylnaltrexone, 8-Hydroxynaltrexone, N-(3-Butenyl)-noroxymorphone, Naltrexone aldol dimer, and N-Formyl-noroxymorphone.

5 . The nal-opioid compound of claim 1 , wherein the nal-opioid is naloxone and the one or more impurities associated with chemical synthesis include 10-Alpha-hydroxynaloxone, 10-Beta-hydroxynaloxone, 10-Ketonaloxone, 3-O-Allylnaloxone, 7,8-Didehydronaloxone, 2,2′-Bisnaloxone, and Naloxone N-oxide.

6 . The nal-opioid compound of claim 1 , wherein the nal-opioid is nalbuphine and the one or more impurities associated with chemical synthesis include Beta-epimer of nalbuphine, 2,2′-Bisnalbuphine, 6-Ketonalbuphine, 10-Ketonalbuphine, Alpha-noroxymorphol, N-(Cyclobutylcarbonyl)-alpha-noroxymorphol, and N-Formyl-6-alpha-noroxymophol.

7 . A nal-opioid compound that contains less of one or more of the following impurities: 15,16-Dehydrobuprenorphine, 17,18-Dehydrobuprenorphine, 18,19-demethylbuprenorphine, 19,19′-Ethylbuprenorphine, 2,2′-Bisbuprenorphine, 3-Dehydroxybuprenorphine, 3-O-Methylbuprenorphine, 3-O-Methyl-N-cyanonorbuprenorphine, 3-O-Methyl-N-methylnorbuprenorphine, 6-O-Desmethylbuprenorphine, Buprenorphine N-oxide, N-But-3-enylnorbuprenorphine, N-But-3-enylnormethylbuprenorphine, N-Butylnorbuprenorphine, N-Methylbuprenorphine, Norbuprenorphine, Tetramethylfuran buprenorphine, 1-Bromooxymorphone, 6-Beta oxymorphol, 10-Alpha-hydroxyoxymorphone, 10-Ketooxymorphone, 2,2-Bisoxymorphone, Noroxymorphone, Oxymorphone N-oxide, 10-Hydroxyoxymorphone, 4-Hydroxyoxymorphone, 8-Hydroxyoxymorphone, Hydromorphinol, 10-Hydroxynaltrexone, 10-Ketonaltrexone, 14-Hydroxy-17-cyclopropylmethylnormorphinone, 2,2′-Bisnaltrexone, 3-Cyclopropylmethylnaltrexone, 3-O-Methylnaltrexone, 8-Hydroxynaltrexone, N-(3-Butenyl)-noroxymorphone, Naltrexone aldol dimer, N-Formyl-noroxymorphone, 10-Alpha-hydroxynaloxone, 10-Beta-hydroxynaloxone, 10-Ketonaloxone, 3-O-Allylnaloxone, 7,8-Didehydronaloxone, 2,2′-Bisnaloxone, Naloxone N-oxide, Beta-epimer of nalbuphine, 2,2′-Bisnalbuphine, 6-Ketonalbuphine, 10-Ketonalbuphine, Alpha-noroxymorphol, N-(Cyclobutylcarbonyl)-alpha-noroxymorphol, or N-Formyl-6-alpha-noroxymophol; as compared to a nal-opioid produced by chemical synthesis.

8 . The nal-opioid compound of claim 7 , wherein the nal-opioid is a buprenorphine compound and it contains less of one or more of the following impurities: 15,16-Dehydrobuprenorphine, 17,18-Dehydrobuprenorphine, 18,19-demethylbuprenorphine, 19,19′-Ethylbuprenorphine, 2,2′-Bisbuprenorphine, 3-Deshydroxybuprenorphine, 3-O-Methylbuprenorphine, 3-O-Methyl-N-cyanonorbuprenorphine, 3-O-Methyl-N-methylnorbuprenorphine, 6-O-Desmethylbuprenorphine, Buprenorphine N-oxide, N-But-3-enylnorbuprenorphine, N-But-3-enylnormethylbuprenorphine, N-Butylnorbuprenorphine, N-Methylbuprenorphine, Norbuprenorphine, or Tetramethylfuran buprenorphine; as compared to chemically synthesized buprenorphinc.

9 . The nal-opioid compound of claim 7 , wherein the nal-opioid is oxymorphone and it contains less of one or more of the following impurities: 1-Bromooxymorphone, 6-Beta oxymorphol, 10-Alpha-hydroxyoxymorphone, 10-Ketooxymorphone, 2,2-Bisoxymorphone, Noroxymorphone, Oxymorphone N-oxide, 10-Hydroxyoxymorphone, 4-Hydroxyoxymorphone, 8-Hydroxyoxymorphone, or Hydromorphinol; as compared to chemically synthesized oxymorphone.

10 . The nal-opioid compound of claim 7 , wherein the nal-opioid is naltrexone and it contains less of one or more of the following impurities: 10-Hydroxynaltrexone, 10-Ketonaltrexone, 14-Hydroxy-17-cyclopropylmethylnormorphinone, 2,2′-Bisnaltrexone, 3-Cyclopropylmethylnaltrexone, 3-O-Methylnaltrexone, 8-Hydroxynaltrexone, N-(3-Butenyl)-noroxymorphone, Naltrexone aldol dimer, or N-Formyl-noroxymorphone; as compared to chemically synthesized naltrexone.

11 . The nal-opioid compound of claim 7 , wherein the nal-opioid is naloxone and it contains less of one or more of the following impurities: 10-Alpha-hydroxynaloxone, 10-Beta-hydroxynaloxone, 10-Ketonaloxone, 3-O-Allylnaloxone, 7,8-Didehydronaloxone, 2,2′-Bisnaloxone, or Naloxone N-oxide; as compared to chemically synthesized naloxone.

12 . The nal-opioid compound of claim 7 , wherein the nal-opioid is nalbuphine and it contains less of one or more of the following impurities: Beta-epimer of nalbuphine, 2,2′-Bisnalbuphine, 6-Ketonalbuphine, 10-Ketonalbuphine, Alpha-noroxymorphol, N-(Cyclobutylcarbonyl)-alpha-noroxymorphol, or N-Formyl-6-alpha-noroxymorphol; as compared to chemically synthesized nalbuphine.