Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
Cancers (Basel) ; 15(24)2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38136388

ABSTRACT

Lung and breast cancers rank as two of the most common and lethal tumors, accounting for a substantial number of cancer-related deaths worldwide. While the past two decades have witnessed promising progress in tumor therapy, developing targeted tumor therapies continues to pose a significant challenge. NAD(P)H quinone oxidoreductase 1 (NQO1), a two-electron reductase, has been reported as a promising therapeutic target across various solid tumors. ß-Lapachone (ß-Lap) and deoxynyboquinone (DNQ) are two NQO1 bioactivatable drugs that have demonstrated potent antitumor effects. However, their curative efficacy has been constrained by adverse effects and moderate lethality. To enhance the curative potential of NQO1 bioactivatable drugs, we developed a novel DNQ derivative termed isopentyl-deoxynyboquinone (IP-DNQ). Our study revealed that IP-DNQ treatment significantly increased reactive oxygen species generation, leading to double-strand break (DSB) formation, PARP1 hyperactivation, and catastrophic energy loss. Notably, we discovered that this novel drug induced both apoptosis and programmed necrosis events, which makes it entirely distinct from other NQO1 bioactivatable drugs. Furthermore, IP-DNQ monotherapy demonstrated significant antitumor efficacy and extended mice survival in A549 orthotopic xenograft models. Lastly, we identified that in mice IP-DNQ levels were significantly elevated in the plasma and tumor compared with IB-DNQ levels. This study provides novel preclinical evidence supporting IP-DNQ efficacy in NQO1+ NSCLC and breast cancer cells.

2.
Article in English | MEDLINE | ID: mdl-37950707

ABSTRACT

Pancreatic cancer is among the top five leading causes of cancer-related deaths worldwide, with low survival rates. Current therapies for pancreatic cancer lack tumor specificity, resulting in harmful effects on normal tissues. Therefore, developing tumor-specific agents for the treatment of pancreatic cancer is critical. NAD(P)H:quinone oxidoreductase 1 (NQO1), highly expressed in pancreatic cancers but not in normal tissues, makes NQO1 bioactivatable drugs a potential therapy for selectively killing NQO1-positive cancer cells. Our previous studies have revealed that novel NQO1 bioactivatable drug deoxynyboquinone (DNQ) is ten-fold more potent than the prototypic NQO1 bioactivatable drug ß-lapachone in killing of NQO1-positive cancer cells. However, DNQ treatment results in high-grade methemoglobinemia, a significant side effect that limits clinical development. Here, we report for the first time on a DNQ derivative, isopentyl-deoxynboquinone (IP-DNQ), which selectively kills pancreatic ductal adenocarcinoma cells in an NQO1-dependent manner with equal potency to the parent DNQ. IP-DNQ evokes massive ROS production and oxidative DNA lesions that results in PARP1 hyperactivation, mitochondrial catastrophe and G2/M-phase arrest, leading to apoptotic and necrotic programmed cell death. Importantly, IP-DNQ treatment causes mild methemoglobinemia in vivo, with a three-fold improvement in the maximum tolerated dose compared to DNQ, while significantly suppresses tumor growth and extends the lifespan of mice in subcutaneous and orthotopic pancreatic cancer xenograft models. Our study demonstrates that IP-DNQ is a promising therapy for NQO1-positive pancreatic cancers and may enhance the efficacy of other anticancer drugs. IP-DNQ represents a novel approach to treating pancreatic cancer with the potential to improve patient outcomes.

4.
Melanoma Res ; 33(6): 514-524, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37738028

ABSTRACT

The treatment of metastatic uveal melanoma remains a major clinical challenge. Procaspase-3, a proapoptotic protein and precursor to the key apoptotic executioner caspase-3, is overexpressed in a wide range of malignancies, and the drug PAC-1 leverages this overexpression to selectively kill cancer cells. Herein, we investigate the efficacy of PAC-1 against uveal melanoma cell lines and report the synergistic combination of PAC-1 and entrectinib. This preclinical activity, tolerability data in mice, and the known clinical effectiveness of these drugs in human cancer patients led to a small Phase 1b study in patients with metastatic uveal melanoma. The combination of PAC-1 and entrectinib was tolerated with no treatment-related grade ≥3 toxicities in these patients. The pharmacokinetics of entrectinib were not affected by PAC-1 treatment. In this small and heavily pretreated initial cohort, stable disease was observed in four out of six patients, with a median progression-free survival of 3.38 months (95% CI 1.6-6.5 months). This study is an initial demonstration that the combination of PAC-1 and entrectinib may warrant further clinical investigation. Clinical trial registration: Clinical Trials.gov: NCT04589832.


Subject(s)
Melanoma , Skin Neoplasms , Uveal Neoplasms , Humans , Animals , Mice , Melanoma/pathology , Uveal Neoplasms/pathology
6.
Cancer Res ; 83(18): 3115-3130, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37522838

ABSTRACT

Several emerging therapies kill cancer cells primarily by inducing necrosis. As necrosis activates immune cells, potentially, uncovering the molecular drivers of anticancer therapy-induced necrosis could reveal approaches for enhancing immunotherapy efficacy. To identify necrosis-associated genes, we performed a genome-wide CRISPR-Cas9 screen with negative selection against necrosis-inducing preclinical agents BHPI and conducted follow-on experiments with ErSO. The screen identified transient receptor potential melastatin member 4 (TRPM4), a calcium-activated, ATP-inhibited, sodium-selective plasma membrane channel. Cancer cells selected for resistance to BHPI and ErSO exhibited robust TRPM4 downregulation, and TRPM4 reexpression restored sensitivity to ErSO. Notably, TRPM4 knockout (TKO) abolished ErSO-induced regression of breast tumors in mice. Supporting a broad role for TRPM4 in necrosis, knockout of TRPM4 reversed cell death induced by four additional diverse necrosis-inducing cancer therapies. ErSO induced anticipatory unfolded protein response (a-UPR) hyperactivation, long-term necrotic cell death, and release of damage-associated molecular patterns that activated macrophages and increased monocyte migration, all of which was abolished by TKO. Furthermore, loss of TRPM4 suppressed the ErSO-induced increase in cell volume and depletion of ATP. These data suggest that ErSO triggers initial activation of the a-UPR but that it is TRPM4-mediated sodium influx and cell swelling, resulting in osmotic stress, which sustains and propagates lethal a-UPR hyperactivation. Thus, TRPM4 plays a pivotal role in sustaining lethal a-UPR hyperactivation that mediates the anticancer activity of diverse necrosis-inducing therapies. SIGNIFICANCE: A genome-wide CRISPR screen reveals a pivotal role for TRPM4 in cell death and immune activation following treatment with diverse necrosis-inducing anticancer therapies, which could facilitate development of necrosis-based cancer immunotherapies.


Subject(s)
Adenosine Triphosphate , TRPM Cation Channels , Mice , Animals , Necrosis/metabolism , Cell Death , Cell Membrane/metabolism , Adenosine Triphosphate/metabolism , Sodium/metabolism , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism
7.
RSC Med Chem ; 13(6): 711-725, 2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35814932

ABSTRACT

Development of targeted anticancer modalities has prompted a new era in cancer treatment that is notably different from the age of radical surgery and highly toxic chemotherapy. Behind each effective compound is a rich and complex history from first identification of chemical matter, detailed optimization, and mechanistic investigations, ultimately leading to exciting molecules for drug development. Herein we review the history and on-going journey of one such anticancer scaffold, the 3-(4-hydroxyphenyl)indoline-2-ones. With humble beginnings in 19th century Bavaria, we review this scaffold's synthetic history and anticancer optimization, including its recent demonstration of tumor eradication of drug-resistant, estrogen receptor-positive breast cancer. Compounds containing the 3-(4-hydroxyphenyl)indoline-2-one pharmacophore are emerging as intriguing candidates for the treatment of cancer.

8.
J Med Chem ; 65(9): 6353-6355, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35467872

ABSTRACT

The Young Medicinal Chemists Committee (YMCC) is a part of the larger ACS Division of Medicinal Chemistry (MEDI) and was formed to ensure that MEDI meets the needs of all medicinal chemists, including students and early career scientists. There is a clear need to offer additional, specific opportunities to this group of medicinal chemists within the MEDI division. Primary functions of YMCC include facilitating networking and mentorship opportunities, collaborating with international medicinal chemistry societies, and offering social programming for all MEDI members at ACS National Meetings. We are excited to continue to engage students and early career chemists through new initiatives and programming in the future. In this Editorial we highlight current initiatives relevant to early career medicinal chemists and solicit input from the larger medicinal chemistry community.


Subject(s)
Chemistry, Pharmaceutical , Humans
9.
Int J Drug Policy ; 103: 103668, 2022 05.
Article in English | MEDLINE | ID: mdl-35367903

ABSTRACT

BACKGROUND: Persons involved with the justice system have an elevated risk of hepatitis C virus (HCV) yet remain marginalized from treatment. Efforts to eliminate HCV will require targeted interventions within the justice system effective at providing diagnosis and treatment. METHODS: We implemented a novel HCV screening and treatment intervention for persons under community supervision in Rhode Island, USA during April 2018--March 2020. Participants received rapid point-of-care HCV antibody testing onsite and referral to community laboratory and treatment services as indicated. We assessed the HCV care cascade to identify areas for improvement. RESULTS: Overall, 483 individuals were screened for HCV antibody; 85 (18%) were positive. A minority of participants with positive HCV antibody tests (n=25/85, 29%) presented to community laboratories for confirmatory testing. Among participants that received HCV viral load results and linked to a treatment provider (n=12), four initiated treatment, three had record of completing treatment, and two were confirmed to have achieved cure. CONCLUSION: Linkage to HCV viral load testing and treatment was challenging in this community supervision population, with substantial loss to follow-up at each step of the HCV cascade. Community supervision remains an important venue for case identification but substantial barriers to accessing HCV treatment exist. Innovative HCV diagnosis and treatment strategies are needed for community supervision populations.


Subject(s)
Hepacivirus , Hepatitis C , Feasibility Studies , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C Antibodies , Humans , Mass Screening/methods
10.
J Med Chem ; 65(5): 3894-3912, 2022 03 10.
Article in English | MEDLINE | ID: mdl-35080871

ABSTRACT

Approximately 75% of breast cancers are estrogen receptor alpha-positive (ERα+), and targeting ERα directly with ERα antagonists/degraders or indirectly with aromatase inhibitors is a successful therapeutic strategy. However, such treatments are rarely curative and development of resistance is universal. We recently reported ErSO, a compound that induces ERα-dependent cancer cell death through a mechanism distinct from clinically approved ERα drugs, via hyperactivation of the anticipatory unfolded protein response. ErSO has remarkable tumor-eradicative activity in multiple ERα+ tumor models. While ErSO has promise as a new drug, it has effects on ERα-negative (ERα-) cells in certain contexts. Herein, we construct modified versions of ErSO and identify variants with enhanced differential activity between ERα+ and ERα- cells. We report ErSO-DFP, a compound that maintains antitumor efficacy, has enhanced selectivity for ERα+ cancer cells, and is well tolerated in rodents. ErSO-DFP and related compounds represent an intriguing new class for the treatment of ERα+ cancers.


Subject(s)
Breast Neoplasms , Estrogen Receptor alpha , Female , Humans , Breast Neoplasms/pathology , Cell Line, Tumor , Estrogen Receptor alpha/metabolism , Receptors, Estrogen/metabolism , Unfolded Protein Response
11.
Sci Transl Med ; 13(603)2021 07 21.
Article in English | MEDLINE | ID: mdl-34290053

ABSTRACT

Metastatic estrogen receptor α (ERα)-positive breast cancer is presently incurable. Seeking to target these drug-resistant cancers, we report the discovery of a compound, called ErSO, that activates the anticipatory unfolded protein response (a-UPR) and induces rapid and selective necrosis of ERα-positive breast cancer cell lines in vitro. We then tested ErSO in vivo in several preclinical orthotopic and metastasis mouse models carrying different xenografts of human breast cancer lines or patient-derived breast tumors. In multiple orthotopic models, ErSO treatment given either orally or intraperitoneally for 14 to 21 days induced tumor regression without recurrence. In a cell line tail vein metastasis model, ErSO was also effective at inducing regression of most lung, bone, and liver metastases. ErSO treatment induced almost complete regression of brain metastases in mice carrying intracranial human breast cancer cell line xenografts. Tumors that did not undergo complete regression and regrew remained sensitive to retreatment with ErSO. ErSO was well tolerated in mice, rats, and dogs at doses above those needed for therapeutic responses and had little or no effect on normal ERα-expressing murine tissues. ErSO mediated its anticancer effects through activation of the a-UPR, suggesting that activation of a tumor protective pathway could induce tumor regression.


Subject(s)
Breast Neoplasms , Neoplasm Recurrence, Local , Animals , Breast Neoplasms/drug therapy , Cell Line , Cell Line, Tumor , Dogs , Estrogen Receptor alpha/metabolism , Female , Humans , Mice , Rats , Unfolded Protein Response
12.
Neoplasia ; 23(8): 811-822, 2021 08.
Article in English | MEDLINE | ID: mdl-34246985

ABSTRACT

Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Herein, we describe our work to include felines and feline oral squamous cell carcinoma (FOSCC) patients in the preclinical assessment process to prioritize lead compounds with increased tolerability and efficacy prior to full human translation. Specifically, our data demonstrate that IB-DNQ, an NQO1-targeted small molecule, is well-tolerated in FOSCC patients and shows promising initial efficacy against FOSCC tumors in proof-of-concept single agent and radiotherapy combination cohorts. Furthermore, FOSCC tumors are amenable to evaluating a variety of target-inducible couplet hypotheses, evidenced herein with modulation of NQO1 levels with palliative radiotherapy. The use of felines and their naturally-occurring tumors provide an intriguing, often underutilized tool for preclinical drug development for NQO1-targeted approaches and has broader applications for the evaluation of other anticancer strategies.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/metabolism , Molecular Targeted Therapy , Mouth Neoplasms/metabolism , NAD(P)H Dehydrogenase (Quinone)/antagonists & inhibitors , Animals , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/etiology , Cats , Combined Modality Therapy , Disease Management , Disease Models, Animal , Drug Evaluation, Preclinical , Humans , Immunohistochemistry , Mice , Mouth Neoplasms/diagnosis , Mouth Neoplasms/drug therapy , Mouth Neoplasms/etiology , Mutation , NAD(P)H Dehydrogenase (Quinone)/genetics , NAD(P)H Dehydrogenase (Quinone)/metabolism , Polymorphism, Single Nucleotide , Tomography, X-Ray Computed , Treatment Outcome
14.
R I Med J (2013) ; 104(3): 53-57, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33789412

ABSTRACT

BACKGROUND: 10-20% of individuals diagnosed with Lyme disease develop chronic symptoms after antibiotic treatment. METHODS: A convenience sample of adults with self- reported, persistent post-Lyme treatment symptoms seeking treatment at the Lifespan Lyme Disease Center in Rhode Island completed a demographic and medical survey, the Patient Reported Outcomes Measurement Information System (PROMIS)-29 v2.0, and other short-form PROMIS measures of cognitive function, sleep disturbance, and fatigue. RESULTS: Compared to average standardized scale scores (T=50; SD=10), participants had mild impairments in physical (T=41) and social (T=42) functioning, mild symptoms of depression (T=56), anxiety (T=60), and sleep disturbance (T=57), and moderate pain interference (T=62), and fatigue (T=65). Participants reported greater symptoms than some other clinical samples including those with cancer and chronic pain. Post-hoc analyses revealed that women reported higher levels of fatigue than men. CONCLUSIONS: People with persistent post-Lyme treatment symptoms report debilitating symptoms and functional impairments which must be considered in clinical care.


Subject(s)
Chronic Pain , Lyme Disease , Adult , Fatigue/epidemiology , Fatigue/etiology , Female , Humans , Lyme Disease/diagnosis , Lyme Disease/drug therapy , Lyme Disease/epidemiology , Male , Quality of Life , Rhode Island/epidemiology
15.
AIDS Behav ; 24(4): 1032-1041, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31004243

ABSTRACT

We recently reported that a 12-week internet weight loss program produced greater weight losses than education control in overweight/obese people living with HIV (PLWH) (4.4 kg vs 1.0 kg; p < 0.05). This manuscript presents the changes in diet, physical activity, behavioral strategies, and cardio-metabolic parameters. Participants (N = 40; 21 males, 19 females) were randomly assigned to an internet behavioral weight loss (WT LOSS) program or internet education control (CONTROL) and assessed before and after the 12-week program. Compared to CONTROL, the WT LOSS arm reported greater use of behavioral strategies, decreases in intake (- 681 kcal/day; p = 0.002), modest, non-significant, increases in daily steps (+ 1079 steps/day) and improvements on the Healthy Eating Index. There were no significant effects on cardio-metabolic parameters. The study suggests that a behavioral weight loss program increases the use of behavioral strategies and modestly improves dietary intake and physical activity in PLWH. Further studies with larger sample sizes and longer follow-up are needed.Clinical Trials Registration: NCT02421406.


Subject(s)
Behavior Therapy , Exercise , Weight Loss , Weight Reduction Programs/statistics & numerical data , Adult , Diet , Female , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Male , Middle Aged , Obesity , Outcome and Process Assessment, Health Care , Overweight
16.
Acta Neuropathol ; 138(6): 1053-1074, 2019 12.
Article in English | MEDLINE | ID: mdl-31428936

ABSTRACT

Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease.


Subject(s)
Brain Neoplasms/metabolism , Epigenesis, Genetic , Glioma/metabolism , Methyltransferases/metabolism , Muscle Proteins/metabolism , Protein Biosynthesis/physiology , Ribosomes/metabolism , Animals , Biomarkers, Tumor , Cell Line, Tumor , DNA Methylation , Humans , Methyltransferases/genetics , Mice, Nude , Muscle Proteins/genetics , Neoplasm Transplantation , RNA, Ribosomal, 28S
17.
ACS Chem Biol ; 14(11): 2335-2348, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31260254

ABSTRACT

Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.


Subject(s)
Caspase 3/genetics , Caspase 3/metabolism , Caspase Inhibitors/chemistry , Neoplasms/therapy , Animals , Apoptosis , Caspase Inhibitors/pharmacology , Cell Death , Cell Line, Tumor , Chelation Therapy/methods , Enzyme Precursors/metabolism , Gene Expression Regulation , Humans , Ligands , Signal Transduction , Zinc/chemistry
18.
Chemistry ; 24(50): 13150-13157, 2018 Sep 06.
Article in English | MEDLINE | ID: mdl-29936701

ABSTRACT

Medium-ring natural products exhibit diverse biological activities but such scaffolds are underrepresented in probe and drug discovery efforts due to the limitations of classical macrocyclization reactions. We report herein a tandem oxidative dearomatization-ring-expanding rearomatization (ODRE) reaction that generates benzannulated medium-ring lactams directly from simple bicyclic substrates. The reaction accommodates diverse aryl substrates (haloarenes, aryl ethers, aryl amides, heterocycles) and strategic incorporation of a bridgehead alcohol generates a versatile ketone moiety in the products amenable to downstream modifications. Cheminformatic analysis indicates that these medium rings access regions of chemical space that overlap with related natural products and are distinct from synthetic drugs, setting the stage for their use in discovery screening against novel biological targets.

19.
Cell Chem Biol ; 25(8): 996-1005.e4, 2018 08 16.
Article in English | MEDLINE | ID: mdl-29909991

ABSTRACT

The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Here we demonstrate a general strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner far superior to combinations with MEK inhibitors. These data suggest the generality of drug-mediated MEK kinase cleavage as a therapeutic strategy to prevent resistance to targeted anticancer therapies.


Subject(s)
Caspase 3/metabolism , Drug Resistance, Neoplasm/drug effects , Enzyme Activation/drug effects , MAP Kinase Kinase Kinases/metabolism , Neoplasms/drug therapy , Proteolysis/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Humans , Leukemia/drug therapy , Leukemia/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , MAP Kinase Kinase Kinases/antagonists & inhibitors , MAP Kinase Signaling System/drug effects , Melanoma/drug therapy , Melanoma/metabolism , Neoplasms/metabolism , Protein Kinase Inhibitors/pharmacology
20.
J Org Chem ; 82(24): 13714-13721, 2017 12 15.
Article in English | MEDLINE | ID: mdl-29206454

ABSTRACT

A facile, gram-scale preparation of 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-ones and 2-hydroxy-6,7,8,8a-tetrahydroindolizin-3(5H)-ones from a condensation cyclization of α-oxoesters with five- and six-membered cyclic imines, respectively, is reported. This transformation enables a concise, three-step synthesis of the natural products phenopyrrozin and p-hydroxyphenopyrrozin. Further, biologically relevant scaffolds, such as α-quaternary ß-homo prolines and ß-lactams, are also prepared in two- to three-steps from the versatile 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one core.


Subject(s)
Heterocyclic Compounds/chemistry , Imines/chemistry , Cyclization , Molecular Structure
SELECTION OF CITATIONS
SEARCH DETAIL
...