Civilians walk past damaged shops as they flee toward safer parts of Manbij, a city in Syria’s Aleppo Governorate, on Aug. 10. (Rodi Said/Reuters)

A fast-moving cataclysm underway in and around Aleppo has brought together all the major actors in Syria’s civil war for what may be the most crucial battle of the five-year conflict, and it is testing whether U.S.-Russian cooperation to end it is a pipe dream.

North of the city — in which the government holds the western side and U.S.-backed moderate opposition forces have occupied the east since 2012 — the opposition has lost control of its only lifeline for resupply under relentless pummeling by Russian and Syrian aircraft and artillery.

The road to Turkey also provided the only path for humanitarian aid or an escape route for at least a quarter-million civilians trapped inside Aleppo, who the United Nations said this week have been left without food, medical supplies or running water.

So dire is their situation that talks initiated by the Obama administration with Russia this summer about coordinating their Syria counterterrorism efforts have been put on the back burner, superseded by urgent negotiations with Moscow over reopening the road to Turkey, according to U.S. officials.

Russia’s U.N. ambassador, Vitaly Churkin, confirmed the negotiations following a closed-door Security Council meeting Tuesday, but he said “certain problems” remained, including Russia’s insistence that no rebel supplies be allowed to pass. So far, progress among the United States, Russia and the United Nations has been slowed by disputes over how far from the road weaponry must be positioned and who would monitor observance of the agreement and man checkpoints.

In Geneva, Russia’s U.N. representative charged that those supporting the opposition were promoting false “hysterics” over the humanitarian situation, Russia’s Interfax news agency reported.

Meanwhile, in Aleppo’s southwestern outskirts, an opposition force dominated by Islamist terrorist fighters, under brutal Syrian and Russian fire, has pushed through a government encirclement to the rebel-controlled part of the city. There, the more moderate opposition fighters now risk being subsumed or driven out by the militants.

The militants appear to have already begun setting up their own judicial councils and aid-distribution networks inside Aleppo, said Hassan Hassan, a Syria expert at the Tahrir Institute for Middle East Policy.

“They want to dominate the area and control the people in it, and they are really trying to boost their legitimacy among the locals by demonstrating their military [power] and winning hearts and minds,” Hassan said of the group now known as Jabhat Fatah al-Sham, or Front for the Conquest of Syria.

Two weeks ago, the Front changed its name from Jabhat al-Nusra and said it was severing its affiliation with al-Qaeda, a move Western officials described as a cosmetic change to mask ulterior motives.

As Front forces increasingly mix with civilians and moderate opposition groups and the remaining civilian population inside the city, the administration’s hopes of separating them and joining Russia in bombing the extremists appear to have dimmed. Overlaps have spread throughout northwest Syria, as moderate fighters — some reluctantly, some less so — have flocked to relationships of convenience with the better-armed and more successful extremists trying to oust President Bashar al-Assad.

That led to the near-collapse of a countrywide cease-fire barely a month after it was negotiated in February by Washington and Moscow, who both had promised to impose it on their Syrian partners on the ground. Only al-Nusra, now the Front, and the Islamic State were exempt. But as Assad’s forces lost ground in continued fighting against al-Nusra, their Russian backers began bombing again. The United States charged that Russia and Assad were using al-Nusra as a smokescreen to strike moderate opposition forces; Russia countered that it was hard to tell them apart.

“We have long been calling on our American partners to influence their proteges in order to stop them . . . associating with al-Nusra, as well as to make it clear where these moderate groups, which have pledged to observe the cessation of hostilities regime, are located,” Alexei Borodavkin, Russia’s representative to U.N. organizations in Geneva, said this week.

Last month, Secretary of State John F. Kerry brought to Moscow a proposal for the United States and Russia to share intelligence, map out where the preponderance of various opposition forces were located, and coordinate in targeting agreed terrorists. The plan, which U.S. officials said gained White House approval over strong Pentagon disagreement, also called for Russia to force Assad to stop his own bombing. Officials spoke on the condition of anonymity about closed-door negotiations with the Russians and the rapidly changing situation on the ground.

A Joint Implementation Group of senior U.S. and Russian military and intelligence officials has now been formed, and maps have been agreed upon.

But, as so often is the case in Syria, events on the ground have outpaced the plan.

First came the Syria-Russia offensive northwest of Aleppo, completing government encirclement and severing of the Castello Road, the only rebel and humanitarian supply route into the eastern half of the city.

Then, last weekend, Front-led opposition fighters on Saturday drove pro-government forces out of Aleppo’s southwestern Ramouseh area. Although the advance raised hopes that supplies to besieged neighborhoods could enter along a southern route, fighting has still been too intense in recently captured areas to allow passage of food and other aid, said Firas Mashhadi, an activist in eastern Aleppo who supports the rebellion.

Mashhadi and others contacted by telephone there said that Russian and government warplanes have intensified attacks in response to rebel gains.

Rebels said they want to expand their assault to the western districts of Aleppo that are controlled by the government. They hope to consolidate their gains before an anticipated counterattack by pro-government forces, including Iraqi Shiite militiamen and fighters from Lebanon’s Hezbollah.

The assault has raised the possibility that opposition forces could impose their own siege on government areas of the city. Such concerns have reportedly caused price increases for food and other goods in government-loyal districts that have until now been largely protected from the fighting.

“Battles are ongoing to secure roads and other entry points to Aleppo, and we are trying to expand areas controlled in the southwestern parts of Aleppo to fortify our positions,” said Capt. Abdulsalam Abdulrazak, spokesman for the Harakat Nour al-Din al-Zenki rebel group that is linked to the umbrella Free Syrian Army.

Abdulrazak criticized the United States for what he called a “lack of support” for opposition forces in Aleppo. Despite calls from inside the administration and from allied governments to step up assistance to the rebels — including antiaircraft equipment that would allow them to challenge the enormous strategic advantage Assad has from his own and Russian planes and helicopters — officials said the White House remains reluctant to do so.

Rebel leaders inside Aleppo, noting the gains that Front-led forces have made in challenging government troops on the ground, and their willingness to endure heavy casualties under withering airstrikes, rejected the notion that the radicals will take over from them.

Adeeb Alsen, of the Jabhat Shamia rebel force, acknowledged that Front troops are participating in the assault. But, he said, “we do not think that it has ambitions of trying to become the dominant force that controls Aleppo for itself.”

Jeff White of the Washington Institute for Near East Policy said the rebel advances in Aleppo underscored the persistent weakness of Assad’s ground troops. “The fundamental problem for the regime is that it can take territory by using its [and Russia’s] firepower, but holding that territory then becomes very difficult,” he said.

Naylor reported from Beirut. Zakaria Zakaria in Istanbul contributed to this report.

Correction: An earlier version of this article misstated comments by Adeeb Alsen, a member of the Jabhat Shamia rebel force. He said fighters with Jabhat Fatah al-Sham are participating in the opposition assault in Aleppo, not leading it. This article has been corrected.