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The reaction of ethyl chloroformate and pyridine with diethylaluminum cyanide as the cyanide source gave the Reissert analog, 1-ethoxycarbonyl-4-cyano-1,4-dihydropyridine and not the expected 1,2-dihydro regio isomer. Under the same conditions, 3-bromopyridine also directly gave the corresponding 1,4-dihydro Reissert analog. Reinvestigation of trimethylsilylcyanide, as the cyanide source, resulted in the observation that both regio isomers are formed and the ratio of these isomers are affected by both solvent polarity and by copper(I) iodide.

Acetate is preferentially transported into and metabolized by astrocytes, rather than synaptosomes or neurons, and labeled acetate is used as a glial reporter molecule to assess glial metabolism and glial-neuronal interactions. Because monocarboxylic acid transporter specificity might confer a phenotype to help localize, detect, and characterize brain tumors of glial origin, use of [2-(14)C]acetate and [(14)C]deoxyglucose (a glucose analog metabolized by all brain cells) was compared in rat and human brain tumors.Cultured C6 glioma or U-373 glioblastoma/astrocytoma tumor cells were injected into the caudate nucleus of anesthetized CDF Fisher rats; 2--3 wk later, an intravenous pulse of [2-(14)C]acetate or [(14)C]deoxyglucose was given, and timed blood samples were drawn during the 5- or 45-min experiment, respectively. Local (14)C levels in the brain were assayed by quantitative autoradiography, and acetate uptake or glucose use was calculated. Uptake and metabolism of the [(14)C]acetate was also assayed in C6 glioma and human surgical tumor samples in vitro.[(14)C]Acetate uptake into rat brain C6 tumors was 9.9 +/- 2.1 mL/100 g/min, compared with 3.9 +/- 1.0 mL/100 g/min in contralateral tissue (n = 6; P0.001), and was much higher than that into other brain structures (e.g., 5:1 for white matter and 2:1 for cortical gray matter). Glucose use in C6 tumors was 111 +/- 34 micromol/100 g/min, versus 81 +/- 5 micromol/100 g/min in contralateral tissue (n = 6; P = 0.08); no left-right differences in glucose use or acetate uptake were seen in other brain structures. The tumor-to-contralateral-tissue ratio for acetate (2.3 +/- 0.3) exceeded that for deoxyglucose (1.4 +/- 0.5) (P0.05), indicating that acetate is a sensitive C6 glioma marker. [(14)C]Acetate uptake also demarcated a few 3-wk-old C6 tumors that had unlabeled necrotic cores. U-373 tumors were smaller than C6 tumors in rat brain and were detected equally well with [(14)C]acetate and [(14)C]deoxyglucose. In vitro uptake of [(14)C]acetate into human glioblastoma or meningioma tumors was higher than uptake into pituitary adenoma. Rat C6 and human tumors with high uptake metabolized acetate to acidic compounds and amino acids.Tumor imaging with radiolabeled acetate can help to localize and classify brain tumors. Transporter and metabolic substrate specificity are traits that can be exploited further for in vivo imaging of brain glial tumors.

The objective was to determine the effects of a recombinant fusion protein anti-GnRH vaccine on testicular development, feedlot performance, and carcass quality of beef bulls. Crossbred beef bulls (n = 58, average weight 306 kg, 9 mo of age), were randomly allocated to two groups and received either an anti-GnRH vaccine (GnRH) or placebo (Control) by intramuscular injection on d 0, 56, and 112. There were group effects (P < 0.01; as a percentage of Control) on testicular weight (53%), daily sperm production (40%), and epididymal sperm reserves (16%). There were group x time interactions (P < 0.0001) for scrotal circumference and serum testosterone concentrations; at slaughter, bulls in the GnRH group had a smaller (P < 0.05) scrotal circumference (28.3 vs 33.9 cm) and lower (P < 0.05) serum testosterone concentrations (2.2 vs 8.6 ng/mL) than those in the Control group. Average daily gain, feed intake, and feed efficiency were not different between treatments during the backgrounding phase (d 0 to 84). During the finishing phase (d 98 to 182), ADG was greater (P < 0.05) for bulls in the Control group (1.69 vs 1.42 kg/d), as was carcass weight (6.9%; P < 0.01). However, GnRH bulls had numerically better feed efficiency (6.12 vs 7.08 kg DMI/kg gain; P < 0.23) and shear force values for ribeye that were 16% lower (P < 0.14) than Control bulls, warranting further investigation. Vaccinating bulls against GnRH suppressed testicular function, with growth and carcass characteristics similar to that expected with steers.

Field data were collected over 2 consecutive years to characterize acute interstitial pneumonia (AIP) in feedyard cattle. Thirty-eight cattle with clinical symptoms of AIP were examined following emergency slaughter; 31 (all heifers) were confirmed to have AIP on the basis of gross and histological lung pathology. The 7 without AIP, plus 17 asymptomatic penmates, were used as contemporary controls. Plasma concentrations of 3-methylindole (3MI) metabolites were higher (P < 0.001) in heifers afflicted with AIP than in the control animals, and concentrations of 3MI mercapturates in the urine were lower (P < 0.007) in affected heifers. Concentrations of 3MI adducts in lung tissue and in microsomal protein did not differ (P > 0.05) between the 2 groups, and 3MI was not detected in ruminal fluid from either group. Total ruminal bacterial numbers and populations of lactobacilli and protozoa were similar (P > 0.05) between the AIP-positive and unafflicted groups, but fewer (P < 0.05) cellulolytic bacteria were present in the positive group. Bovine respiratory syncytial virus antigen was not found in lung tissue from any of the heifers confirmed to have AIP. To our knowledge, this study is the first to implicate 3MI metabolites as having a role in feedyard AIP. Further research is required to determine the factors responsible for the elevation in 3MI adducts in plasma and urine of feedyard cattle afflicted with AIP.

A number of observations including clinical manifestation, course, outcome, and family history, support the view that patients presenting with a major depression occurring first in late life should be treated as a nosological subgroup. In this study quantitative magnetic resonance imaging (MRI) was used to investigate volumes of different brain structures in 19 patients with late onset major depression (age of onset50) and 13 age matched controls. 3-D MRI sequences were acquired using a Siemens 1.5T scanner. Whole brain volume, CSF volume, volume of the frontal and temporal lobes and the volume of the amygdala-hippocampus complex were assessed using the software NMRWin. Compared to the controls, depressed patients showed a significantly lower whole brain volume and a significantly higher CSF volume, whereas volumes of the frontal and temporal lobes as well as the amygdala-hippocampus complex volumes were not significantly decreased. In addition, depressed patients exhibited a higher ventricle-brain ratio suggesting a higher degree of central atrophy compared to healthy individuals. Our results indicate that cerebral changes involving subcortical structures are of relevance in the pathogenesis of late-onset depression. Defining the aetiology of these lesions may be important for the development of preventive treatment of depression in the elderly.

The involvement of melengestrol acetate (MGA) in susceptibility to developing pulmonary edema and emphysema following oral administration of 3-methylindole (3MI) was investigated using 10 Suffolk ewes receiving 0 or 0.15 mg of MGA daily (n = 5). Blood, urine and ruminal fluid were collected immediately prior to 3MI dosing (0.2 g/kg BW) and 1, 2, 3, 4, 5, 6, 12 and 24 h (blood); 3, 6, 9, 12 and 15 h (urine) and 1, 2, 3 and 12 h (ruminal fluid) afterward. Ewes receiving MGA experienced earlier (P < 0.05) onset of respiratory distress than the control ewes (2.5 vs 4 h), and upon euthanasia at 96 h, their lung weight relative to body weight tended (P < 0.10) to be lower. Ruminal 3MI concentrations did not differ between treatments (P > 0.05). Ewes receiving MGA had higher (P < 0.05) concentrations of 3MI metabolites in plasma prior to dosing than did control ewes, and these values tended to remain higher throughout the sampling period. Immunoreactivity assays indicated more pneumotoxin present in the lungs of MGA-treated ewes than controls. Lung damage was apparently more acute and accelerated in the MGA-treated ewes than in the controls. Urinary 3MI mercapturate concentrations differed (control > MGA-treated, P < 0.05) at 9, 12, and 15 h, but this difference was not apparent when urinary production (as estimated by creatinine concentration) was considered. The implications of these findings for MGA-treated feedlot heifers are currently under investigation.

Improvements in feedlot management practices and the use of various feed additives have reduced, but not eliminated, the occurrence of bloat in feedlot cattle. Feedlot bloat reduces the profitability of production by compromising animal performance and more directly by causing fatalities. In feedlots, bloat is associated with the ingestion of large amounts of rapidly fermented cereal grain and destabilization of the microbial populations of the rumen. An abundance of rapidly fermented carbohydrate allows acid-tolerant bacteria (e.g., Streptococcus bovis and Lactobacillus spp.) to proliferate and produce excessive quantities of fermentation acids. As a result, ruminal pH becomes exceedingly low, and this impairs rumen motility. Further, the excessive production of mucopolysaccharide or "slime" increases the viscosity of ruminal fluid and stabilizes the foam implicated in frothy feedlot bloat. Although protocols have been developed to treat feedlot bloat, the most profitable approach is to use management strategies to reduce its likelihood. Amount of roughage, grain processing techniques, selection of cereal grain (e.g., corn, barley, and wheat), dietary adaptation periods, and various additives (e.g., ionophores) can influence the occurrence of bloat in feedlot cattle. Successful management of these factors depends on a thorough understanding of the behavioral, dietary, and microbial events that precipitate bloat in feedlot cattle.

Viele Befunde weisen darauf hin, das Patienten mit einer erstmals im hoheren Lebensalter auftretenden Depression als nosologische Subgruppe innerhalb der affektiven Erkrankungen zu betrachten sind (6). So besitzen Familienmitglieder von Spatdepressiven (Ersterkrankungsalter >50 Jahre) kein erhohtes Morbiditats-risiko fur affektive Erkrankungen, was auf eine geringere Bedeutung der genetischen Pradisposition bei dieser Patientengruppe hinweist (3). Neuropathologische Studien legen nahe, das strukturelle zerebrale Veranderungen bei alteren depres-siven Patienten haufig sind (2), was als Hinweis auf das Vorliegen eines „organi-schen” Faktors bei der Entstehung der Satdepression gewertet werden kann.

Introduction NMDA receptor ligands have been shown to rapidly treat depression but are associated with psychotomimetic effects. GLYX-13 is an NMDA receptor glycine site functional partial agonist with ~ 25% of the agonist activity of glycine or Dserine. Animal models suggest a single intravenous dose may produce long-term efficacy without psychotomimetic effects. Objective A phase II randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy of GLYX-13 with central raters. Aim To examine the effects of a single dose of GLYX-13 in subjects with inadequate response to previous treatment for MDD. Methods 48 male and 68 female subjects received a single dose of GLYX-13 (1-/5-/10-/30-mg/kg) or placebo. Central raters assessed subjects via telephone using the HDRS-17 at Screening, Baseline, Days 1, 3, 7, 14, 21 and 28. Results The a priori primary efficacy ANCOVA on pooled drug dose versus placebo was not significant for change from baseline to Day 1 on HDRS-17 total score. MMRM revealed a statistically significant reduction in HDRS-17 total score versus placebo at Day 3 for 5-mg/kg (−4.4; p Conclusion This study suggests that GLYX-13, an NMDA receptor glycine site functional partial agonist, rapidly reduces depression scores without eliciting psychotomimetic effects at therapeutic doses as assessed by central raters. Further study is indicated.

Introduction Centralized ratings by telephone have proven feasible for assessment of psychiatric diagnosis, symptom severity, and suicidality, and may be used for safety assessments in non-psychiatric trials with sites that do not employ staff experienced in psychiatric assessment. Objective To assess whether centralizing assessments with mental health experts enables immediate clinical follow-up and actionable diagnostic support for investigators. Aims To examine the feasibility of centralized ratings in a Phase III dermatology clinical trial for safety assessments. Methods 1127 subjects enrolled in a trial of medication for their dermatologic condition were assessed via telephone by central raters who administered the SCID-CT, C-SSRS and PHQ-8 at screening. At monthly visits, central raters performed the C-SSRS, PHQ-8, GAD-7 and items designed to detect emergent psychotic symptoms. Results: Screening 34 subjects were excluded on the basis of SCID-CT diagnosis. Based on diagnosis or severity, subjects were classified as being in no need of mental health services, having mild psychiatric symptoms (referred to local mental health service provider; n=33), moderate (immediate referral for psychiatric evaluation; n=17), or severe (immediate escort to emergency room; n=0). One subject reported suicidal ideation on the C-SSRS, 10 reported self-injurious behavior, and 5 reported suicidal behavior in the last year. Follow-Up No subjects reported suicidal ideation or behavior at any of the 6861 follow-up assessments. One subject reported self-injurious behavior and two reported emergent psychotic symptoms. Conclusions This study established the feasibility and acceptability of routine screening and monitoring of psychopathology and suicidality by central raters in a non-psychiatric population.

Introduction Negative syndromes in Schizophrenia are of increasing interest to drug developers. Several assessment strategies have emerged for identifying negative symptoms including the NSA-16, PANSS negative symptom subscale and the Marder subscale. Assessment of patients with schizophrenia by videoconferencing has been shown to yield results equivalent to those obtained when the scale is administered face-to-face. Objectives To assess remote assessment of negative symptoms including blinding to protocol details and visit number, effectively eliminating enrollment and expectation biases. Aims To assess whether negative symptom scales can be reliably assessed in a clinical trial by videoconferencing. Methods The PANSS and the NSA-16 were administered to 227 subjects with schizophrenia in a randomized clinical trial via live videoconferencing by 17 blinded independent central raters. Subjects were interviewed at screen, at 11 more visits over 36 weeks, and at endpoint or 1 year. On a subset of subjects, a senior clinician observed and independently rated the PANSS and NSA as a quality control measure. Results ICCs between raters and observing trainers were .98 on the NSA total score (N = 65 pairs) and .96 on the PANSS total score (N = 69 pairs). ICCs of individual NSA items ranged from .72-1.0, with a mean ICC of .91. ICCs of PANSS subscales ranged from .94 -.96 with ICCs of .95 for the Marder subscale and .94 for the negative subscale. Conclusion Excellent item-level ICCs for the NSA suggest that negative symptoms can be rated reliably by videoconferencing using well-calibrated blinded independent raters.

Introduction Expectation bias (EB) occurs when an individual's expectations about an outcome influence perceptions of one's own or others’ behavior. In clinical trials, both raters and subjects may enter trials with expectations. Rater EB occurs when raters expect that subjects will improve over the course of the trial. Subject EB occurs when subjects themselves expect to get better. Rater and subject expectations can interact to create a therapeutic alliance. Objectives To examine the impact of EB on placebo response and drug-placebo separation. Aims To identify methods for avoiding expectation bias in CNS clinical trials. Methods We review eight studies that illustrate the problem of rater and subject EB across therapeutic areas. Results Studies examining rater EB suggest it can affect diagnosis and decrease IRR when subjects do not behave according to expectations. Studies of subject EB suggest subject expectations can increase placebo response and affect study outcome. Studies of the interaction of rater and subject expectations find placebo response increases with number of follow-up visits, and having a different rater for baseline, endpoint, and sequential visits may decrease placebo response. Conclusions Patient expectations, rater expectations, and rater-patient relationships can increase placebo response and decrease signal detection. Blinding raters to protocol details, including entry criteria and visit number, reduces expectations of improvement. Using different raters at baseline, endpoint and consecutive visits reduces the possibility that relationship bias could influence ratings. Utilizing remote, independent raters is one means to adequately blind and vary raters.

Introduction Inappropriate subjects may be enrolled in a study when enrollment pressures cause inflated baseline severity scores. An increasing number of studies now include methods such as blinded independent centralized ratings (CR) to ensure that appropriate subjects are entered into the trial. Post-baseline factors such as functional unblinding, expectation bias and rater drift can also affect outcomes. Objectives Independent raters, blind to study visit, can minimize functional unblinding and expectation bias. Continuous calibration of CR can minimize rater drift. Aims To examine studies with both site ratings (SR) and CR to determine how critical post-baseline blinding and continuous calibration are. Methods A trial of acute schizophrenia used CR for the PANSS and SR for the BPRS on the same subjects. A Parkinson's psychosis study used CR in the US and SR ex-US to assess subjects using the SAPS. A GAD trial used CR of subjects enrolled by SRs’ SIGH-A evaluations. Results In the schizophrenia trial, CR separated the active comparator and one of two test arms. SR separated the active comparator but neither test arm. In the Parkinson's psychosis study, pimavanserin showed greater separation with CR than SR. In the GAD trial, CR had lower placebo response than SR, independent of subject selection. Conclusions Data from several studies support the continued importance of rater blinding and independence, post subject selection. Results suggest that precision of ratings beyond baseline can increase the sensitivity of findings in a clinical trial, decrease placebo response rates and potentially eliminate Type II errors.

Abstract 1059 Aims: Genetic lesions are crucial for cancer initiation. Recently, whole genome sequencing using next generation technology was used as a systematic approach to identify mutations in genomes of various types of tumors including melanoma, lung and breast cancer as well as cytognetically normal acute myeloid leukaemia (CN-AML). Despite its technical feasibility, whole genome sequencing is still time consuming and cost intensive. As an alternative approach, here we identify tumor-specific somatic mutations by sequencing transcriptionally active genes. Methods: Mutations were detected by comparing the transcriptome sequence of a CN-AML with the corresponding remission sample. In a single Genome Analyzer II run, we generated 4.35 Gbp of CN-AML and 5.54 of remission transcriptome sequence from the same patient. 63% of AML reads and 74% of remission reads mapped to exon regions. 10,152 genes had an average read depth of at least 7-fold and 6,989 genes an average read depth of 20 or greater in both samples. By comparing the 8,978 coding Single Nucleotide Variants (SNVs) discovered in the CN-AML sample with the remission sample, we identified 5 non-synonymous mutations specific to the tumor sample. Results: We found 5 tumor-specific somatic mutations. Among them is a nonsense mutation affecting the RUNX1 gene, which is a frequent mutational target in AML, and a missense mutation in the putative tumor suppressor gene TLE4, which encodes a RUNX1 interacting protein. A second missense mutation was identified in SHKBP1, which acts downstream of FLT3, a receptor tyrosine kinase mutated in about 30% of AML cases. The frequency of mutations in TLE4 and SHKBP1 in a cohort of 95 CN-AML patients was 2%. Conclusion: Our study demonstrates that whole transcriptome sequencing leads to the rapid detection of recurring point mutations in the coding regions of genes relevant to malignant transformation. Disclosures: No relevant conflicts of interest to declare.

2-Methylindazole undergoes 1, 4-addition on treatment under Reissert conditions. Methylation of the product in strong base leads to 2, 3-dimethylindazole.

Reissert compounds and analogs were synthesized from the reaction of an acid halide, heterocyclic base and diethylaluminum cyanide. This new method of Reissert compound synthesis gave yields comparable to other synthetic routes

The phthalazine Reissert compound has been used to convert phthalazine to 1-benzylphthalazines, bisbenzylphthalazines, 1,4-disubstituted phthalazines, 1-cyanophthalazine, and a number of other phthalazine derivatives including the tricyclic compound 14.

The condensation of the anion of isoquinoline Reissert compounds with diaryl ethers is reported. These condensation products are converted into analogues of bis-benzylisoquinoline alkaloids.

A number of C-acetyl heterocyclic compounds were condensed with isatin and substituted isatins to give a series of 3-hydroxy-3-substituted oxindoles. The products from 2-acetylfuran and isatin, 2-acetylthiophene and isatin, and 2-acetylpyridine and 1-methylisatin were active at 100 mg/Kg in the maximal electroshock seizure test.

□ Cyclohexanone, substituted cyclohexanones, and other cycloalkanones have been condensed with isatin and substituted isatins to give a series of new 3-hydroxy-3-substituted oxindoles. A number of these 3-hydroxyoxindoles possess anticonvulsant activity.

It has been reported that a population of cells from mouse bone marrow migrates to supernatant made from the incubation of minced fragments of new-born mouse thymuses and that the migrated population is enriched for immature lymphoid cells. In the present study, we show that this method enriches for thymic-homing cells. Migration-enriched cells were labelled with fluorescein isothiocyanate (FITC) and were injected into the tail veins of lethally irradiated mice. Cell suspensions of the thymuses from these experimental mice had 8.1 +/- 1.8% fluorescing cells compared to control mice given equal numbers of non-migration-enriched FITC labelled cells which had 2.4 +/- 1.7% positive cells.

Present theories suggest two classes of excitation processes which may be responsible for the observed amplitudes of solar p-mode oscillations—self-excitation of the modes via an overstability mechanism such as the K mechanism 2, and stochastic excitation by turbulent convection2–4. We now have data which stand in support of the latter mechanism. Linear overstability calculations are still ambiguous, because of the uncertainties involved in including turbulent viscous damping of the modes. Nevertheless no calculation predicts overstable f-modes, and these modes are observed on the Sun. Furthermore no nonlinear damping mechanism has yet been proposed which would limit the growth of overstable modes to their observed amplitudes. Assuming the modes are stably damped, the theory of mode excitation by convective turbulence now gives mode amplitudes that are in agreement with observations4. In this letter we use data from Big Bear Solar Observatory to compare theory and observation in detail. In particular, our data show that the energy per oscillation mode is nearly constant at low mode frequencies, and is approximately independent of degree at low degrees. The total energy in all the oscillation modes is estimated at ∼1034erg.

The anion of isoquinoline Reissert Compounds has been condensed with 4-piperidones and pyridinecarb-oxaldehydes to give esters which are easily hydrolyzed to alcohols. The anticonvulsants activity of these alcohols is reported and several are active in the maximal electroshock seizure test.

The phthalazine Reissert compound hydrofluoroborate undergoes condensation with alkynes to give pyrrolo[2,1-α]phthalazines and with alkenes to give 2-(1-phthalazyl)pyrroles. The phthalazine Reissert compound undergoes acid catalyzed condensations with some alkenes but the intermediate is of sufficient stability to be isolated. This same type of intermediate can also be isolated in the acid-catalyzed hydrolysis of the phthalazine Reissert compound.

(1975). THE SYNTHESIS OF SOME NEW DIARYL ETHERS. Organic Preparations and Procedures International: Vol. 7, No. 4, pp. 193-199.

Quinazoline, acid chlorides, and trimethylsilyl cyanide have been converted to mono-Reissert compounds at the 3,4-position of the quinazoline system. Various reactions of these quinazoline Reissert compounds are reported.

The hydrazides of benzoic, phenyacetic, and 3-phenylpropionic acids react with an acidic solution of formaldehyde to give 15. Similar treatment of the corresponding methylhydrazides gave 16. The ethers 15 can be cleaved to give, after methylation, 16. Spectral data for 15 and 16 are presented.

Various di-Reissert compounds and analogs were prepared from quinazoline by use of trimethylsilyl cyanide together with a catalytic amount of anhydrous aluminum chloride. Reactions of these quinazoline di-Reissert compounds are reported.

From the viewpoint of nature conservation, a number of demands are formulated in respect to forestry. In private forests, many of these wishes ― yet not all of them ― are fulfilled automatically as many large private forestry enterprises managed in accordance with the laws of nature have proved in the past. For the remaining services, private forest owners should be offered programs that are similar to those for landscape preservation of the Bavarian Ministry for the Environment, or respective plans of the Bavarian Ministry of Agriculture for farmers. Under such conditions, demands of nature conservation towards forestry could be fulfilled not only by the state forests but also on private woodlands without economical losses by their owners

The synthesis of several new isoquinoline Reissert compounds is described. Alkylation reactions of the anions of these new Reissert compounds and a rearrangement reaction are reported.

The title compounds have been prepared by the cyclocondensation of 3-mercaptopropanoic acid with isat-in-3-imines. The 1-benzyl derivatives have been synthesized by simultaneously reacting 1-benzylisatin, substituted anilines and 3-mercaptopropanoic acid. Mannich condensation of the spiro thiazanones with secondary amines gave the corresponding 1-aminomethyl derivatives.

The title compounds have been prepared by the cyclocondensation of mercaptosuccinic acid with isatin-3-imines. The 1-benzyl derivatives have been synthesized by simultaneously reacting 1-benzylisatin, substituted anilines and mercaptosuccinic acid. The structure of the products has been confirmed by X-ray diffraction measurements.

Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method. Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.

3,4-Dihydro-β-carboline and benzo[α]-γ-carboline yielded Reissert compounds. The 3,4-dihydro-β-carboline Reissert compound, through its acid- and base-promoted reactions, was found to be a very useful intermediate in the synthesis of several β-carboline derivatives including tetracyclic compounds. Reaction of the 3,4-dihydro-β-carboline Reissert compound with dichlorodicyanobenzoquinone (DDQ) resulted in the formation of l-cyano-β-carboline thereby providing the first example of an oxidation of a Reissert compound with DDQ. α-, β- and γ-Carbolines failed to form Reissert compounds under a wide variety of conditions. 7-Azaindole also failed to yield a Reissert compound.

Ellipticine and a number of ellipticine analogs were converted to Reissert compounds. Alkylation of the 6-benzylellipticine Reissert compound gave a series of 1-substituted-6-benzylellipticines. 1-Cyanoellipticine, obtained through the Reissert compound, was hydrolyzed to ellipticine-1-carboxamide hydrochloride which was active against P388 lymphocytic leukemia. Other aspects of the chemistry of the ellipticine Reissert compound are presented.