Synthesis and characterization of macrocyclic bisphosphonate dimers
Bibliographic record
Abstract
Abstract Background : Attempts to optimize the synthetic yield of known macrocyclic phosphonates resulted in the discovery of two new macrocyclic bisphosphonate dimers. Methods : An attempt was carried out to optimize the yield of a known macrocyclic bisphosphonate dimer, 6 , over the yield of monomers 2 and 3 , using the Mitsunobu protocol in the macrocyclization step. Cyclization reactions were carried out at 0.003 M, 0.004 M, 0.005 M, 0.008 M and 0.02 M, compared to 0.002 M in our initial report of the synthesis of monomers. Results : In this attempt to optimize the production of dimer 6 , two new macrocyclic diastereomers of 6 , namely 28-membered bisphosphonates 9 and 10 , were isolated in yields of 3% and 2%, respectively, and characterized by FTIR, LC-MS, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:oasis="http://docs.oasis-open.org/ns/oasis-exchange/table" altimg="e1.gif" display="inline" overflow="scroll"> <mml:msup> <mml:mrow> <mml:mtext /> </mml:mrow> <mml:mrow> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> <mml:mstyle mathvariant="normal"> <mml:mi>H</mml:mi> </mml:mstyle> </mml:math>, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:oasis="http://docs.oasis-open.org/ns/oasis-exchange/table" altimg="e2.gif" display="inline" overflow="scroll"> <mml:msup> <mml:mrow> <mml:mtext /> </mml:mrow> <mml:mrow> <mml:mn>1</mml:mn> <mml:mn>3</mml:mn> </mml:mrow> </mml:msup> <mml:mstyle mathvariant="normal"> <mml:mi>C</mml:mi> </mml:mstyle> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:oasis="http://docs.oasis-open.org/ns/oasis-exchange/table" altimg="e3.gif" display="inline" overflow="scroll"> <mml:msup> <mml:mrow> <mml:mtext /> </mml:mrow> <mml:mrow> <mml:mn>3</mml:mn> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> <mml:mstyle mathvariant="normal"> <mml:mi>P</mml:mi> </mml:mstyle> </mml:math> NMR as well as by X-ray crystallography. Conclusions : The results described herein further illustrate the utility of the Mitsunobu macrocyclization (ring-closing) reaction toward the synthesis of macrocyclic phosphonates. The X-ray crystallographic characterization of the three bisphosphonate dimers, together with correlations to specific <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:oasis="http://docs.oasis-open.org/ns/oasis-exchange/table" altimg="e4.gif" display="inline" overflow="scroll"> <mml:msup> <mml:mrow> <mml:mtext /> </mml:mrow> <mml:mrow> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> <mml:mstyle mathvariant="normal"> <mml:mi>H</mml:mi> </mml:mstyle> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:oasis="http://docs.oasis-open.org/ns/oasis-exchange/table" altimg="e5.gif" display="inline" overflow="scroll"> <mml:msup> <mml:mrow> <mml:mtext /> </mml:mrow> <mml:mrow> <mml:mn>3</mml:mn> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> <mml:mstyle mathvariant="normal"> <mml:mi>P</mml:mi> </mml:mstyle> </mml:math> NMR resonances allowed for the assignments of relative stereochemistries between the various dimers.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".